New-4-pyrrolopyrimidin-6-YL)benzenesulphonamide derivatives

ABSTRACT

This invention is directed to selective antagonists of A 2A  and/or A 2B  adenosine receptors having the general formula (I); to processes for their preparation; to pharmaceutical compositions comprising them; and to their use in therapy.

The present invention relates to new antagonists of A_(2A) and A_(2B)adenosine receptors. These compounds are useful in the treatment,prevention or suppression of diseases and disorders known to besusceptible of being improved by antagonism of A_(2A) and/or A_(2B)adenosine receptors, such as Parkinson's disease, asthma, allergicdiseases, inflammation, atherosclerosis, hypertension, gastrointestinaltract disorders, cell proliferation disorders and autoimmune diseases.

Adenosine regulates several physiological functions through specificcell membrane receptors, which are members of the G-prqtein coupledreceptor family. Four distinct adenosine receptors have been identifiedand classified: A₁, A_(2A), A_(2B) and A₃.

A_(2A) adenosine receptors are mainly found in the brain (striatum,nucleus accumbens and olfactory bulb), platelets, leukocytes, spleen andthymus (see Fredholm et al. Pharmacol Rev. 2001, 53 (4), 527-552).Adenosine A_(2A) receptors modulate the release of GABA in the striatum.Thus, A_(2A) receptor antagonists are a useful alternative for thetreatment for Parkinson's disease (Mally, J. and Stone, T. W., CNSDrugs, 1998, 10, 311-320) and for other neurodegenerative diseases. Thepharmacology of A_(2A) adenosine receptors has been reviewed by Onginiet al. in Trends Pharmacol Sci. 1996, 17(10), 364-372.

The A_(2B) adenosine receptor subtype (see Feoktistov, I., Biaggioni, I.Pharmacol. Rev 1997, 49, 381-402) has been identified in a variety ofhuman and murine tissues and is involved in the regulation of vasculartone, smooth muscle growth, angiogenesis, hepatic glucose production,bowel movement, intestinal secretion, and mast cell degranulation.

In view of the physiological effects mediated by adenosine receptoractivation, several A_(2A) and/or A_(2B) receptor antagonists have beenrecentity disclosed for the treatment or prevention of Parkinson'sdisease, Alzheimer disease, Huntington chorea, Wilson's disease, asthma,bronchoconstriction, allergic diseases, hypertension, atherosclerosis,reperfusion injury, myocardial ischemia, retinopathy, inflammation,gastrointestinal tract disorders, cell proliferation diseases and/ordiabetes mellitus. See for example WO 01/16134, WO 01/02400, WO 01/80893or WO 00/73307.

It has now been found that certain4-(pyrrolopyrimidin-6-yl)benzenesulphonamide derivatives are new potentand selective antagonists of A_(2A) and A_(2B) adenosine receptors andcan therefore be used in the treatment or prevention of these diseases.

Further objectives of the present invention are to provide a method forpreparing said compounds; pharmaceutical compositions comprising aneffective amount of said compounds; the use of the compounds in themanufacture of a medicament for the treatment of pathological conditionsor diseases susceptible of being improved by antagonism of A_(2A) and/orA_(2B) adenosine receptors; and methods of treatment of pathologicalconditions or diseases susceptible to amelioration by antagonism ofA_(2A) and/or A_(2B) adenosine receptors comprising the administrationof the compounds of the invention to a subject in need of treatment.

Thus, the present invention is directed to new6-(4-aminosulphonylphenyl)-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dionederivatives of formula (I)

wherein

R¹ and R² each independently represent:

a hydrogen atom;

a hydrocarbon chain selected from an alkyl, alkenyl or alkynyl group,which is optionally substituted by one or more, for example 1, 2, 3 or4, substituents selected from halogen, hydroxy, alkoxy, alkylthio,amino, monoalkylamino, dialkylamino, cyano, oxo, hydroxycarbonyl,alkoxycarbonyl, acylamino, carbamoyl, alkylcarbamoyl,dihydroxyphosphoryloxy or dialkoxyphosphoryloxy groups;

or a group of formula—(CH₂)_(n)-R⁶

-   -   wherein n is an integer from 0 to 4 and R⁶ represents a 3- to        7-membered aromatic or non-aromatic cyclic group containing from        0 to 4 heteroatoms selected from N, O and S, which is optionally        bridged and/or fused to another 3- to 7-membered aromatic or        non-aromatic cyclic group containing from 0 to 4 heteroatoms        selected from N, O and S;

the cyclic groups in the moiety R⁶ being optionally substituted by oneor more, for example 1, 2, 3 or 4, R⁷ substituents selected fromhalogen, alkyl, alkenyl, alkynyl, aryl, arylalkyl, cycloalkyl,heteroaryl, heteroarylalkyl, heterocydyl, hydroxy, alkylenedioxy,alkoxy, alkylthio, amino, monoalkylamino, dialkylamino, nitro, cyano,oxo, hydroxycarbonyl, alkoxycarbonyl, acylamino, carbamoyl,alkylcarbamoyl, dihydroxyphosphoryloxy and dialkoxyphosphoryloxy groups;

the hydrocarbon chains and the cyclic moieties of these R⁷ substituentsbeing optionally substituted by one or more, for example 1, 2, 3 or 4,further R⁶ substituents selected from halogen, hydroxy, oxo, cyano,alkyl, difluoromethyl, trifluoromethyl, alkoxy, alkylenedioxy,alkylthio, acylamino, carbamoyl, alkylcarbamoyl, dihydroxyphosphoryloxy,dialkoxyphosphoryloxy, hydroxyalkoxy, phenyl, alkoxycarbonyl, amino,monoalkylamino, dialkylamino and hydroxycarbonyl groups;

R³ represents a hydrogen or halogen atom, or a nitro, alkoxycarbonyl oralkyl group; the alkyl group being optionally substituted by one ormore, for example 1, 2, 3 or 4, substituents selected from hydroxy,alkoxy, alkylthio, amino, monoalkylamino, dialkylamino, hydroxycarbonyl,alkoxycarbonyl, acylamino, carbamoyl or alkylcarbamoyl groups;

R⁴ and R⁵ are the same or different, each independently representing:

hydrogen;

a group of formula —(CH₂)n-R⁶, wherein n is an integer from 0 to 4; andR⁶ is as defined above and is optionally substituted by one or more, forexample 1, 2, 3 or 4, R⁷ substituents, wherein R⁷ is as defined aboveand is optionally substituted by one or more, for example 1, 2, 3 or 4,further R⁸ substituents. wherein R⁸ is as defined above;

or a hydrocarbon chain selected from alkyl, alkenyl or alkynyl, which isoptionally substituted by one or more, for example 1, 2, 3 or 4,substituents selected from —(CH₂)_(n)-R⁶, —O—(CH₂)_(n)-R⁶,—S—(CH₂)_(n)-R⁶, —NH—(CH₂)_(n)-R⁶, hydroxy, oxo, halogen, alkoxy,alkylthio, amino, monoalkylamino, and dialkylamino groups; the alkylchains in the alkoxy, alkylthio, monoalkylamino and dialkylaminosubstituents being optionally substituted by one or more, for example 1,2, 3 or 4, further substituents selected from —(CH₂)_(n)-R⁶, hydroxy,oxo, halogen, alkoxy, alkylthio, amino, monoalkylamino and dialkylaminogroups; and wherein each n is independently an integer from 0 to 4 andeach R⁶ is as defined above and is optionally substituted by one ormore, for example 1, 2, 3 or 4, R⁷ substituents, wherein R⁷ is asdefined above and is optionally substituted by one or more, for example1, 2, 3 or 4, further R⁶ substituents, wherein R⁸ is as defined above;

or, alternatively, R⁴ and R⁵, together with the nitrogen atom to whichthey are attached, form a 3- to 7-membered aromatic or non-aromaticcyclic group comprising from 1 to 4 heteroatoms selected from N, O andS, which is optionally bridged and/or fused to another 3 to 7-memberedaromatic or non-aromatic cyclic group containing from 0 to 4.heteroatoms selected from N, O and S; the cyclic groups being optionallysubstituted by one or more, for example 1, 2, 3 or 4, substituentsselected from —(CH₂)_(n)-R⁶ and R⁷; the hydrocarbon chains and thecyclic moieties of the R⁷ substituents being optionally substituted byone or more, for example 1, 2, 3 or 4, further substituents selectedfrom —(CH₂)_(n)-R⁶ and R⁸; and the alkyl chains in the R⁵ substituentsbeing optionally substituted by one or more, for example 1, 2, 3 or 4,further substitutents selected from —(CH₂)_(n)-R⁶, hydroxy, halogen,alkoxy, alkylthio, amino, monoalkylamino and dialkylamino groups;wherein each of the R⁶ substituents is optionallly substitued by one ormore, for example 1, 2, 3 or 4, R⁷ substituents and each of these R⁷substituents is optionally substituted by one or more, for example 1, 2,3 or 4, R⁸ substituents; and wherein each n, R₆, R⁷ and R⁸ is as definedabove.

or an N-oxide or a pharmaceutically acceptable salt thereof.

As used herein, a hydrocarbon chain is a straight or branched non-cylicsequence of carbon atoms covalently linked by single, double or triplebonds, and substituted by hydrogen atoms. for example straight orbranched alkyl alkenyl or alkynyl groups, moieties or chains. Typically,the hydrocarbon chains contain from 1 to 10 carbon atoms. As usedherein, an alkyl, alkenyl or alkynyl group or moiety is a straight orbranched group or moiety. Typically it is a C₁-C₁₀ group or moiety, forexample a C₁-C₆ group or molety, preferably a C₁-C₄ group or moiety.Examples include methyl, ethyl. i-propyl, n-propyl, n-butyl, t-butyl,allyl, 2-propenyl and 3-butynyl. Where a group contains two or morealkyl, alkenyl or alkynyl moieties, these moieties may be the same ordifferent. When an alkyl, alkenyl or alkynyl chain, group or moietycarries 2 or more substituents, the substituents may be the same ordifferent

As used herein, an alkylene group or moiety is a divalent alkyl moietytypically having from 1 to 6, for example from 1 to 4, carbon atoms.Examples of C₁-C₄ aalkylene groups include methylene, ethylene,propylene and butylene groups. When an alkylene or alkylenedioxy groupis present as a substituent on another group it shall be deemed to be asingle substituent, rather than a group formed by two substituents.

As used herein, the alkyl chains present in the arylalkyl,heteroarylalkyl, alkoxy, alkylthio, monoalkylamino, dialkylamino,hydroxyalkoxy, alkoxycarbonyl, alkylcarbamoyl, alkylenedioxy anddialkoxyphosphoryloxy groups are typically straight or branched alkylchains containing from 1 to 6 carbon atoms.

As used herein, an acyl group or moiety typically has from 2 to 7 carbonatoms. Thus, it is typically a group of formula —COR wherein R is ahydrocarbon chain group having from 1 to 6 carbon atoms. Preferably, itis a group of formula —COR wherein R is a C₁-C₆ alkyl group.

As used herein, an aryl group or moiety is typically a C₆-C₁₀ aryl groupor moiety such as phenyl or naphthyl. Phenyl is preferred. When an arylgroup or moiety carries 2 or more substituents, the substituents may bethe same or different.

As used herein, a heteroaryl group or moiety is typically a 5- to10-membered aromatic ring, such as a 5- or 6-membered ring, containingat least one heteroatom selected from O, S and N. Examples includepyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, furanyl, oxadiazolyl,oxazolyl, imidazolyl, thiazolyl, thiadiazolyl, thienyl, pyrazolidinyl,pyrrolyl and pyrazolyl groups. Oxadiazolyl, oxazolyl, pyridyl, pyrrolyl,imidazolyl, thiazolyl, thiadiazolyl, furanyl, thienyl, pyrazinyl andpyrimidinyl groups are preferred. When a heteroaryl group or moietycarries 2 or more substituents, the substituents may be the same ordifferent.

As used herein, a cycloalkyl group typically has from 3 to 6 carbonatoms. Examples include cyclopropyl, cyclobutyl, cyclopentyl andcyclohexyl. It is preferably cyclopropyl, cyclopentyl or cyclohexyl.When a cycloalkyl group carries 2 or more substituents, the substituentsmay be the same or different.

As used herein, a heterocydyl group is typically a non-aromatic,saturated or unsaturated C₃-C₁₀ carbocydic ring in which one or more,for example 1, 2, 3 or 4 of the carbon atoms are replaced by aheteroatom selected from N, O and S. Saturated heterocydyl groups arepreferred. Examples of suitable heterocyclyl groups include piperidinyl,piperazinyl, morpholinyl, 4,5-dihydro-oxazolyl, 3-aza-tetrahydrofuranyl,imidazoildinyl and pyrrolidinyl groups. Where a heterocyclyl groupcarries 2 or more substituents, the substituents may be the same ordifferent.

As used herein, a halogen atom, is typically a chlorine, fluorine orbromine atom.

As used herein, some of the atoms, groups, moieties, chains or cyclespresent in the general structures of the invention are “optionallysubstituted”. This means that these atoms, groups, moieties, chains orcycles can be either unsubstituted or substituted by one or more, forexample 1, 2, 3 or 4, substituents, whereby the hydrogen atoms bound tothe unsubstituted atoms, groups, moieties, chains or cycles are replacedby chemically acceptable atoms, groups, moieties, chains or cycles.Typically when a cyclic group is bridged by an alkylene group, thebridging alkylene group is attached to the ring at non-adjacent atoms.

Compounds of the formula (I) containing one or more chiral centre may beused in enantiomerically or diastereoisomerically pure form, or in theform of a mixture of isomers.

As used herein, a pharmaceutically acceptable salt is a salt with apharmaceutically acceptable acid or base. Pharmaceutically acceptableacids include both inorganic acids, for example hydrochloric, sulphuric,phosphoric, diphosphoric, hydrobromic and nitric acid and organic acids,for example citric, fumaric, maleic, malic, ascorbic, succinic,tartaric, benzoic, acetic, methanesulphonic, ethanesulphonic,benzenesulphonic or p-toluenesulphonic acid. Pharmaceutically acceptablebases include alkali metal (e.g. sodium or potassium) and alkali earthmetal (e.g. calcium or magnesium) hydroxides and organic bases, forexample alkyl amines, aralkyl amines and heterocyclic amines.

As used herein, an N-oxide is formed from the tertiary basic amines orpyridines present in the molecule, using a convenient oxidising agent.

Preferred compounds of the invention are those wherein R¹ and R² areindependently an alkyl group optionally substituted by one or more, forexample 1, 2, 3 or 4, substituents selected from hydroxy, halogen,alkoxy, alkylthio, amino, monoalkylamino, dialkylamino, hydroxycarbonyl,and alkoxycarbonyl groups; or a group of formula —(CH₂)_(n)R⁶, wherein nis an integer from 0 to 2 and R⁶ represents a 3- to 7-membered aromaticor non-aromatic cyclic group having from 0 to 2 heteroatoms selectedfrom nitrogen and oxygen. More preferred compounds are those wherein thealkyl chains, moieties or groups present R¹ and R² are C₁-C₆ alkylchains, moieties or groups. Most preferably, R¹ and R² are bothunsubstituted C₁-C₆ alkyl groups.

Further preferred compounds of the invention are those wherein R³represents hydrogen or a halogen atom, more preferably hydrogen or achlorine atom, most preferably hydrogen.

Also preferred are compounds wherein R⁴ is as defined above and R⁵ ishydrogen, a group of formula —(CH₂)_(n)-R⁶ or a hydrocarbon chainselected from alkyl, alkenyl and alkynyl, which is optionallysubstituted by one or more, for example 1, 2, 3 or 4, groups selectedfrom —(CH₂)_(n)-R⁶ and —(CH₂)_(n)-O-R⁶; each R⁶ebeing a phenyl or apyridyl group, which is optionally substituted by one or more, forexample 1, 2, 3 or 4, substituents selected from halogen, hydroxy,alkyl, alkoxy and alkylthio groups. More preferred compounds are thosewherein R⁵ is hydrogen, alkyl or benzyl. Most preferred compounds arethose wherein R⁵ is hydrogen or alkyl.

Typically, R⁴ is:

hydrogen;

a group of formula —(CH₂)_(n)-R⁶, wherein n is 0, 1 or 2 and R⁶ is a 5-to 7-membered aromatic or non-aromatic cyclic group containing 0 to 2heteroatoms selected from N, O and S, which is optionally substituted byone or more, for example 1, 2, 3 or 4, R⁷ substituents selected fromhalogen, alkyl, alkenyl, alkynyl, aryl, arylalkyl, cycloalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, hydroxy, alkylenedioxy,alkoxy, alkylthio, amino, monoalkylamino, dialkylamino, nitro, cyano,oxo, hydroxycarbonyl, alkoxycarbonyl, acylamino, carbamoyl,alkylcarbamoyl, dihydroxyphosphoryloxy and dialkoxyphosphoryloxy groups;the hydrocarbon chains and the cyclic moieties of these R⁷ substituentsbeing optionally substituted by one or more, for example 1, 2, 3 or 4,further R⁸ substituents selected from halogen, hydroxy, oxo, cyano,alkya trifluoromethyl, alkoxy, alkylenedioxy, alkylthio, acylamino,carbamoyl, alkylcarbamoyl, dihydroxyphosphoryloxy,dialkoxyphosphoryloxy, hydroxyalkoxy, phenyl, alkoxycarbonyl, amino,monoalkylamino, dialkylamino and hydroxycarbonyl groups; or

an alkyl, alkenyl or alkynyl chain, which is optionally substituted byone or more, for example 1, 2, 3 or 4, substituents selected from—(CH₂)_(n)-R⁶, —O—(CH₂)_(n)-R⁶, —S—(CH₂)_(n)-R⁶, —NH—(CH₂)_(n)-R⁶,hydroxy, oxo, halogen, alkoxy, alkylthio, amino, monoalkylamino, anddialkylamino groups; the alkyl chains in the alkoxy, alkylthio,monoalkylamino and dialkylamino substituents being optionallysubstituted by one or more, for example 1, 2, 3 or 4, furthersubstituents selected from —(CH₂)_(n)-R⁶, hydroxy, oxo, halogen, alkoxy,alkylthio, amino, monoalkylamino and dialkylamino groups; and whereineach n is independently an integer from 0 to 4 and each R⁶ is isindependenty a 5- or 6-membered aromatic or non-aromatic cyclic grouphaving 0, 1 or 2 heteroatoms selected from N, O and S, and is optionallysubstituted by one or more, for example 1, 2, 3 or 4, R⁷ substituents,wherein R⁷ is as defined above and is optionally substituted by one ormore, for example 1, 2, 3 or 4, further R⁸ substituents, wherein R⁸ isas defined above;

More preferably, R⁴ is:

hydrogen;

a group of formula —CH₂)_(n)-R⁶ wherein n is 0, 1 or 2 and R⁶ is a 5- to6-membered heteroaryl or heterocyclyl group containing up to 2heteroatoms selected from N, O and S, for example a piperidinyl,pyrrolidinyl or pyridyl group, which is optionally substituted by a R⁷substituent selected from halogen, alkyl, alkoxy, arylalkyl orheteroarylalkyl groups, the aryl and heteroaryl moieties of thesearylalkyl and heteroarylalkyl R⁷ substituents being optionallysubstituted by 1 or 2 further R⁸ substituents selected from halogen,cyano, alkyl, trifluoromethyl, alkoxy and alkylenedioxy; or

an alkyl group which is optionally substituted by 1 or 2 substituentsselected from amino monoalkylamino, dialkylamino, —OR⁶ and —SR⁶substituents, wherein R⁶ is a 5- or 6-membered heteroaryl groupcontaining 1 or 2 heteroatoms, for example a pyridyl group, and isoptionally substituted by one or more R⁷ substituents selected fromhydroxy, halogen, amino, monoalkylamino, dialkylamino, cyano,hydroxycarbonyl, alkoxycarbonyl, alkoxy, alkylenedioxy and alkylthio;and wherein the alkyl chains of each of the said monoalkylamino anddialkylamino substituents are optionally substituted by 1 or 2 furthersubstituents selected from a hydroxy group and a group of formula—CH₂)_(n)-R⁶, wherein n is an integer from 0 to 4 and R⁶ is an arylgroup, for example a benzyl group.

Most preferably, R⁴ is:

a group of formula —(CH₂)_(n)-R⁶ wherein n is 0, 1 or 2 and R⁶ is a 5-to 6-membered heteroaryl or heterocyclyl group containing up to 2 Natoms, for example a piperidinyl, pyrrolidinyl or pyridyl group, whichis optionally substituted by a R⁷ substituent selected from halogen,alkyl, alkoxy, arylalkyl or heteroarylalkyl groups, the aryl andheteroaryl moieties of these arylalkyl and heteroarylalkyl R⁷substituents being optionally substituted by 1 or 2 further R⁸substituents selected from halogen and alkoxy; or

an alkyl group which is optionally substituted by 1 or 2 substituentsselected from monoalkylamino, dialkylamino, —OR⁶ and —SR⁶ substituents,wherein R⁶ is a 5- or 6-membered heteroaryl group containing 1 or 2 Natoms, for example a pyridyl group, and is optionally substituted by oneor more R⁷ substituents selected from halogen and alkoxy; and whereinthe alkyl chains of each of the said monoalkylamino and dialkylaminosubstituents are optionally substituted by 1 or 2 further substituentsselected from a hydroxy group and a group of formula —(CH₂)_(n)-R⁶,wherein n is an integer from 0 to 4 and R⁶ is an aryl group, for examplea benzyl group.

In other preferred embodiments of the invention R⁴ and R⁵ form, togetherwith the nitrogen atom to which they are attached, an optionally bridged5- to 7-membered aromatic or non-aromatic cyclic group which contains upto two nitrogen atoms, and which is optionally substituted by a group offormula —(CH₂)_(n)-R⁶ or by a R⁷ substituent selected from alkyl,alkenyl and alkynyl chains; the said alkyl, alkenyl and alkynyl chainsbeing optionally substituted by one or more, for example 1, 2, 3 or 4,groups of formula —(CH₂)_(n)-R⁶ or R⁸ substituents selected fromhydroxy, halogen, alkoxy, alkylthio, amino, monoalkylamino, anddialkylarmino groups; the alkyl chains in these R⁸ substituents beingoptionally substituted by one or more, for example 1, 2, 3 or 4, furthersubstituents selected from a group of formula —(CH₂)_(n)-R⁶, andhydroxy, halogen, alkoxy, alkylthio, amino, monoalkylamino anddialkylamino groups; wherein each of the R⁶ groups is optionalllysubstitued by one or more, for example 1, 2, 3 or 4, R⁷ substituents andeach of these R⁷ substituents is optionally substituted by one or more,for example 1, 2, 3 or 4, R⁸ substituents; each n, R⁶, R⁷ and R⁸ beingas defined above.

More preferably, R⁴ and R⁵ form, together with the N atom to which theyare attached, a 5- , 6- or 7-membered saturated heterocyclic group whichcontains 1 or 2 nitrogen atoms and which optionally carries a bridgingalkylene group (for example a piperazinyl, homopiperazinyl, or2,5-methanopiperazinyl group), said cyclic group being optionallysubstituted by a group of formula —(CH₂)_(n)-R⁶ wherein n is 0, 1 or 2and R⁶ is a 5- or 6-membered aromatic or non-aromatic ring containing 0,1 or 2 heteroatoms selected from N, O and S (for example, a phenyl,furanyl, thienyl, pyridyl or pyrimidinyl ring), or by a R⁷ substituentselected from alkyl and alkenyl groups, the group R⁶ being optionallysubstituted by 1, 2 or 3 further substituents selected from haloalkyl,alkyl, alkoxy, alkylenedioxy, cyano and halogen groups, and the said R⁷substituent being optionally substituted by 1 or 2 phenyl substituents.

Particular individual compounds of the invention include:

6-[4-(4-Benzylpiperazine-1-sulphonyl)phenyl]-1,3-dimethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

6-{4-[4-(4-Fluorobenzyl)piperazine-1-sulphonyl]phenyl}-1,3-dimethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

6-{4-[4-(3-Fluorobenzyl)piperazine-1-sulphonyl]phenyl}-1,3-dimethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

6-{4-[4-(2,4-Difluorobenzyl)piperazine-1-sulphonyl]phenyl}-1,3-dimethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

6-{4-[4-(2-Fluorobenzyl)piperazine-1-sulphonyl]phenyl}-1,3-dimethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

6-{4-[4-(4-Chlorobenzyl)piperazine-1-sulphonyl]phenyl}-1,3-dimethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

6-{4-[4-(3-Chlorobenzyl)piperazine-1-sulphonyl]phenyl}-1,3-dimethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

6-{4-[4-(4-Bromobenzyl)piperazine-1-sulphonyl]phenyl}-1,3-dimethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

6-{4-[4-(2-Bromobenzyl)piperazine-1-sulphonyl]phenyl}-1,3-dimethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

1,3-Dimethyl-6-{4-[4-(4-trifluoromethylbenzyl)piperazine-1-sulphonyl]phenyl}1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

6-{4-[4-(4-tert-Butylbenzyl)piperazine-1-sulphonyl]phenyl}-1,3-dimethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

6-{4-[4-(4-Methoxybenzyl)piperazine-1-sulphonyl]phenyl}-1,3-dimethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

6-{4-[4-(3-Methoxybenzyl)piperazine-1-sulphonyl]phenyl}-1,3-dimethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

6-[4-(4-Benzo[1,3]dioxol-5-ylmethylpiperazine-1-sulphonyl)phenyl]-1,3-dimethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

4-{4-[4-(1,3-Dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6]pyrimidin-6-yl)benzenesulphonyl]piperazin-1-ylmethyl}benzonitrile

6-[4-(4-Furan-3-ylmethylpiperazine-1-sulphonyl)phenyl]-1,3-dimethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

1,3-Dimethyl-6-[4-(4-thiophen-2-ylmethylpiperazine-1-sulphonyl)phenyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

6-{4-[4-(5-Chlorothiophen-2-ylmethyl)piperazine-1-sulphonyl]phenyl}-1,3-dimethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

1,3-Dimethyl-6-[4-(4-pyridin-4-ylmethylpiperazine-1-sulphonyl)phenyl]-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

1,3-Dimethyl-6-{4-[4-(1-phenylethyl)piperazine-1-sulphonyl]phenyl}-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

6-[4-(4-Benzyl-[1,4]diazepane-1-sulphonyl)phenyl]-1,3-dimethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

6-{4-[4-(4-Fluorobenzyl)[1,4]diazepane-1-sulphonyl]phenyl}-1,3-dimethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

1,3-Dimethyl-6-{4-[4-((E)-3-phenylallyl)piperazine-1-sulphonyl]phenyl}-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

6-[4-((1S,4S)-5-Benzyl-2,5-diazabicyclo[2.2.1]heptane-2-sulphonyl)phenyl]-1,3-dimethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

6-[4(4-Benzhydrylpiperazine-1-sulphonyl)phenyl]-1,3-dimethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

N-[2-(Benzylmethylamino)ethyl]-4-(1,3-dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulphonamide

1,3-Dimethyl-6-[4-(4-pyridin-2-yl-piperazine-1-sulphonyl)-phenyl]-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

6-{4-[4-(5-Methoxypyrimidin-4-yl)piperazine-1-sulphonyl]phenyl}-1,3-dimethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

N-(1-Benzylpiperidin-4-yl)-4-(1,3-dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulphonamide

4-(1,3-Dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-[1-(4-fluorobenzyl)piperidin-4-yl]benzenesulphonamide

N-[1-(3,4-Dimethoxybenzyl)piperidin-4-yl]-4-(1,3-dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulphonamide

4-(1,3-Dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-(1-thiophen-2-ylmethylpiperidin-4-yl)benzenesulphonamide

N-(1-Benzylpiperidin-4-yl)-4-(1,3-dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-methylbenzenesulphonamide

N-(1-Benzylpyrrolidin-3-yl)-4-(1,3-dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulphonamide

N-(1-Benzylpyrrolidin-3-yl)-4-(1,3-dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-methylbenzenesulphonamide

4-(1,3-Dimethyl-2,4dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-(6-methoxypyridin-3-yl)benzenesulphonamide

4-(1,3-Dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-(2-pyridin-2-ylethyl)benzenesulphonamide

4-(1,3-Dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-pyridin-2-ylbenzenesulphonamide

4-(1,3-Dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-(5-methylpyridin-2-yl)benzenesulphonamide

1,3-Dimethyl-6-[4-(4-phenylpiperazine-1-sulphonyl)phenyl]-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

1,3-Dimethyl-6-{4-[4-(4-trifluoromethylphenyl)piperazine-1-sulphonyl]-phenyl}-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

6-{4-[4-(3,5-Dichloropyridin-4-yl)piperazine-1-sulphonyl]phenyl}-1,3-dimethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

6-[4-(4-Benzylpiperazine-1-sulphonyl)phenyl]-1,3-diethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

1,3-Diethyl-6-{4-[4-(4-fluorobenzyl)piperazine-1-sulphonyl]phenyl}-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

1,3-Diethyl-6-{4-[4-(3-fluorobenzyl)piperazine-1-sulphonyl]phenyl}-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

6-{4-[4-(2,4-Difluorobenzyl)piperazine-1-sulphonyl]phenyl}-1,3-diethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

6-{4-[4-(4-Chlorobenzyl)piperazine-1-sulphonyl]phenyl}-1,3-diethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

6-{4-[4-(3-Chlorobenzyl)piperazine-1-sulphonyl]phenyl}-1,3-diethyl-1,5-dihydropyrrolo[3,2-d]pynimidine-2,4-dione

6-{4-[4-(4-Bromobenzyl)piperazine-1-sulphonyl]phenyl}-1,3-diethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

6-{4-[4-(2-Bromobenzyl)piperazine-1-sulphonyl]phenyl}-1,3-diethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

1,3-Diethyl-6-{4-[4-(4-trifluoromethylbenzyl)piperazine-1-sulphonyl]phenyl}-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

6-{4-[4-(4-tert-Butylbenzyl)piperazine-1-sulphonyl]phenyl}-1,3-diethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

1,3-Diethyl-6-{4-[4-(4-methoxybenzyl)piperazine-1-sulphonyl]phenyl}-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

1,3-Diethyl-6-{4-[4-(3-methoxybenzyl)piperazine-1-sulphonyl]phenyl}-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

6-[4-(4-Benzo[1,3]dioxol-5-ylmethylpiperazine-1-sulphonyl)phenyl]-1,3-diethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

4-{4-[4-(1,3-Diethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulphonyl]piperazin-1-ylmethyl}benzonitrile

1,3Diethyl-6-[4-(4-furan-2-ylmethylpiperazine1-sulphonyl)phenyl]-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

1,3Diethyl-6-[4-(4thiophen-2-ylmethylpiperazine-1-sulphonyl)phenyl]-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

6-{4-[4-(5-Chlorothiophen-2-ylmethyl)piparazine-1-sulphonyl]phenyl}-1,3-diethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4dione

1,3Diethyl4-6-[4-(4-pyridinyl-4-methylpiperazine1-sulphonyl)phenyl]-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

1,3-Diethyl-6-{4-[4-(1-phenylethyl)piperazine-1-sulphonyl]phenyl}-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

1,3Diethyl-6-{4-[4-(4-fluorobenzyl-[1,4]diazepane1-sulphonyl]phenyl}-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

1,3Diethyl-6-[4-(4-phenethylpiperazine-1-sulphonyl)phenyl]-1,5dihydropyrrolo[3,2-d]pyrimidine-2,4dione

6-[4-((1S,4S-5-Benzyl-2,5-diazabicyclo[2.2.1]heptane-2-sulphonyl)phenyl]-1,3-diethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

N-[2-(Benzylmethylamino)ethyl]-4(diethyldioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulphonamide

N-{2-[Benzyl-(2-hydroxyethyl)amino]ethyl}-4-(diethyldioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimiding-6-yl)benzenesulphonamide

1,3Diethyl-6-[4-(4-pyridin-2-ylpiperazine-1-sulphonyl)phenyl]-1,5dihydropyrrolo[3,2-d]pyrimidine-2,4dione

N-(1-Benzylpiperidin-4-yl)-4-(1,3-diethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulphonamide

4-(1,3-Diethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-[1-(4-fluorobenzyl)piperidin-4-benzenesulphonamide

4-(1,3-Diethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-[1-(3,4-dimethoxybenzyl)piperidin-4-yl]benzenesulphonamide

4-(1,3-Diethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-(1-thiophen-2-ylmethylpiperidin-4-yl)benzenesulphonamide

N-(1-Benzylpiperidin-4yl)-4-(1,3-diethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-methylbenzenesulphonamide

N-(1-Benzylpyrrolidin-3-yl)-4-(1,3-diethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulphonamide

N-(1-Benzylpyrrolidin-3-yl)(1,3diethyl-2,4dioxo2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pydimidin-6-yl)-N-methylbenzenesulphonamide

4-(1,3-Diethyl-2,4dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-dipyrimidin-6-yl)N-(2-pyridin-2-yl-ethyl)benzenesulphonamide

6-[4-(4-Benzylpiperazine-1-sulphonyl)phenyl]-1,3-dipropyl-1,5-dihydro-pyrrolo[3,2-d]pyrimidine-2,4-dione

6-{4-[4-(4-Fluorobenzyl)piperazine-1-sulphonyl]phenyl}-1,3-dipropyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

6-{4-[4-(3-Fluorobenzyl)piperazine-1-sulphonyl]phenyl}1,3-dipropyl-1,5-dihydropyrrolo[3,2-d]pydimidine-2,4-dione

6-{4-[4-(2,4-Difluorobenzyl)piperazine-1-sulphonyl]phenyl}-1,3dipropyl-1,5-dihydropyrrolo[3,2-d]pydimidine-2,4-dione

6-{4-[4-(4-Chlorobenzyl)piperazine-1-sulphonyl]phenyl}-1,3-dipropyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

6-{4-[4-(3-Chlorobenzyl)piperazine-1-sulphonyl]phenyl}1,3-dipropyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

6-{4-[4-(4-Bromobenzyl)piperazine-1-sulphonyl]phenyl}-1,3-dipropyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

6-{4-[4-(2-Bromobenzyl)piperazine-1-sulphonyl[phenyl}-1,3-dipropyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

1,3-Dipropyl-6-{4-[4-(4-trifluoromethylbenzyl)piperazine-1-sulphonyl]phenyl}-1,5-dihydropyrrolo[3,2-d]pydimidine-2,4-dione

6-{4-[4-(4-tert-Butylbenzyl)piperazine-1-sulphonyl]phenyl}-1,3-dipropyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

6-{4-[4-(4-Methoxybenzyl)piperazine-1-sulphonyl]phenyl)-1,3-dipropyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

6-{4-[4-(3-Methoxybenzyl)piperazine-1-sulphonyl]phenyl}-1,3-dipropyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

6-[4-(4-Benzo[1,3]dioxol-5-ylmethylpiperazine-1-sulphonyl)phenyl]-1,3-dipropyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

4-{4-[4-(2,4-Dioxo-1,3dipropyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulphonyl]piperazin-1-ylmethyl}benzonitrile

1,3-Dipropyl-6-[4-(4-thiophen-2-ylmethylpiperazine-1-sulphonyl)phenyl]-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

6{4-[4-(5-Chlorothiophen-2-ylmethyl)piperazine-1-sulphonyl]phenyl}-1,3-dipropyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

1,3-Dipropyl-6-[4-(4-pyridin-4-ylmethylpiperazine-1-sulphonyl)phenyl]-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

6-{4-[4(1-Phenylethyl)piperazine-1-sulphonyl]phenyl}-1,3-dipropyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

6-{4-[4-(4-Fluorobenzyly[1,4]diazepane-1-sulphonyl]phenyl}-1,3-dipropyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

6-[4-(4-Phenethylpiperazine-1-sulphonyl)phenyl]-1,3-dipropyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

1,3-Dipropyl-6-[4-(4-pyridin-2-ylpiperazine-1-sulphonyl)pheny1]-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

N-(1-Benzylperidin-4-yl)-(2,4-dioxo-1,3-dipropyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulphonamide

4-(2,4-Dioxo-1,3-dipropyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-[1-4-fluorobenzylpiperidin-4-yl]benzenesulphonamide

N-[1-(3,4-Dimethoxybenzyl)piperidin-4-yl]-4-(2,4-dioxo-1,3-dipropyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulphonamide

4-(2,4-Dioxo-1,3-dipropyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-(1-thiophen-2-yl-methylpiperidin-4-yl)benzenesulphonamide

N-(1-Benzylpiperidin-4-yl)-4-(2,4-dioxo-1,3-dipropyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-methylbenzenesulphonamide

N-(1-Benzylpyrrolidin-3-yl)4-(2,4-dioxo-1,3-dipropyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulphonamide

4-(2,4-Dioxo-1,3-dipropyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-(6-methoxypyridin-3-yl)benzenesulphonamide

4-(2,4-Dioxo-1,3-dipropyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-(2-pyridin-2-yl-ethyl)benzenesulphonamide

4-(2,4Dioxo-1,3-dipropyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-pyridin-2-ylbenzenesulphonamide

6-[4-(4-Benzylpiperazine-1-sulphonyl)phenyl]-1-methyl-3-propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

6-{4-[4-(4-Fluorobenzyl)piperazine-1-sulphonyl]phenyl}-1-methyl-3-propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

6-{4-[4-(3Fluorobenzyl)piperazine-1-sulphonyl]phenyl}-1-methyl-3propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

6-{4-[4-(2,4-Difluorobenzyl)piperazine-1-sulphonyl]phenyl}-1-methyl-3propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

6-{4-[4-(4-Chlorobenzyl)piperazine-1-sulphonyl]phenyl}-1-methyl-3-propyl1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

6-{4-[4-(3-Chlorobenzyl)piperazine-1-sulphonyl]phenyl}-1-methyl-3-propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

6-{4-[4-(4-Bromobenzyl)piperazine-1-sulphonyl]phenyl}-1-methyl-3propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

6-{4-[4-(2-Bromobenzyl)piperazine-1-sulphonyl]phenyl}-1-methyl-3propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

1-Methyl-3propyl-6-{4-[4-(4-trifluoromethylbenzyl)piperazine-1-sulphonyl]phenyl}-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

6-{4-[4-(4-tert-Butylbenzyl)piperazine-1-sulphonyl]phenyl}-1-methyl-3propyl1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

6-{4-[4-(4-Methoxybenzyl)piperazine-1-sulphonyl]phenyl}-1-methyl-3-propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

6-{4-[4-(3-Methoxybenzyl)piparazine-1-sulphonyl]phenyl}-1-methyl-3-propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

6[4-(4-Benzol[1,3]dioxol-5-ylmethylpiperazine-1-sulphonyl)phenyl-1-methyl-3propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

4-{4-[4-(1-Methyl-2,4-dioxo-3-propyl2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulphonyl]piperazin-1-ylmethyl}benzonitrile

6-[4-(4-Furan-3-ylmethylpiperazine-1-sulphonyl)phenyl[-1-methyl-3-propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

1-Methyl-3-propyl-6-[4-(4-thiophen-2-ylmethylpiperazine1-1-sulphonyl)phenyl]-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

6-{4-[4-(5-Chlorothiophen-2-ylmethyl)piperazine-1-sulphonyl]phenyl}-1-methyl-3-propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

1-Methyl-3-propyl-6-[4-(4pyridin-4-ylmethylpiperazine-1-sulphonyl)phenyl]-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

6{4-[4-(4-Fuorobenzyl)-[1,4]diazepane-1-sulphonyl]phenyl}-1-methyl-3propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

N-[2-(Benzylmethylamino)ethyl]-4-(methyldioxopropyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulphonamide

1-Methyl-3-propyl-6-[4-(4-pyridin-2-yipiperazine-1-sulphonyl)phenyl]-1,5-dihydropyrrolo[3,2-d]pyrimidin-2,4-dione

N-(1-Benzylpiperidin-4yl)-4-(1-methy-2,4-dioxopropyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6yl)benzenesulphonamide

N-[1-(4-Fluoroenzyl)piperidin-4-yl]-4-(1-methyl-2,4-dioxo-3-propyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin6-yl)benzenesulphonamide

N-[1-3,4Dimethoxybenzyl)piperidin-4-yl]-4-(1-methyl-2,4-dioxo-3-propyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6yl)benzenesulphonamide

4-(1-Methyl-2,4-dioxo-3-propyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-(1-thiophen-2-ylmethylpiperidin-4-yl)benzenesulphonamide

N-(1-Benzylpiperdin-4-yl)-N-methyl-4-(1-methyl-2,4dioxopropyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulphonamide

4-(1-Methyl-2,4-dioxo-3-propyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-(2-pyridin-2-ylethyl)benzenesulphonamide

6-[4-(4-Benzylpiperazine-1-sulphonyl)phenyl]-3-methyl-1-propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

6-{4-[4-(4-Fluorobenzyl)piperazin-1-sulphonyl]phenyl}-3-methyl-1-propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

6-{4-[4-(3-Fluorobenzyl)piperazin-1-sulphonyl]phenyl}-3-methyl-1-propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

6-{4-[4-(4-Chlorobenzyl)piperazin-1-sulphonyl]phenyl}-3-methyl-1-propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

6-{4-[4-(3-Chlorobenzyl)piperazin-1-sulphonyl]phenyl}-3-methyl-1-propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

6-{4-[4-(4-Bromobenzyl)piperazin-1-sulphonyl]phenyl}-3-methyl-1-propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

6-{4-[4-(2-Bromobenzyl)piperazin-1-sulphonyl]phenyl}-3-methyl-1-propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

3-Methyl-1-propyl-6-{4-[4-(4trifluoromethylbenzyl)piperazine-1-sulphonyl]phenyl}-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

6-{4-[4-(4-tert-Butylbenzyl)piperazine-1-sulphonyl]phenyl}-3-methyl-1-propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

6-{4-[4-(4-Methoxybenzyl)piperazine-1-sulphonyl]phenyl}-3methyl-1-propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

6-{4-[4-(3-Methoxybenzyl)piperazine-1-sulphonyl]phenyl}-methyl-1-propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

6-[4(4Benzol[1,3]dioxol-5-ylmethylpiperazine-1-sulphonyl)phenyl]-3-methyl-1-propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

4-{4-[4-(3-Methyl-2,4-dioxo-1-propyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulphonyl]piperazin-1-ylmethyl}benzonitrile

3-Methyl-1-propyl-6-[4-(4-thiophen-2-ylmethylpiperazine-1-sulphonyl)phenyl]-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

6-{4-[4-(5-Chlorothiophen-2-ylmethyl)piperazine-1-sulphonyl]-phenyl}-3-methyl-1-propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

3-Methyl-1-propyl-6-[4-(4-pyridin-4-ylmethylpiperazine-1-sulphonyl)phenyl]-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

3-Methyl-6-{4-[4-(1-phenylethyl)piperazine-1-sulphonyl]-phenyl}-1-propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2.4-dione

6-[4-(4-Benzyl[1,4]diazepane-1-sulphonyl)phenyl]-3-methyl-1-propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

6-{4-[4-(4-Fluorobenzyl)[1,4]diazepane-1-sulphonyl]-phenyl}-methyl-1-propyl-1,5-dihydropyrrolo[3.2-d]pyrimidine-2,4-dione

3-Methyl-6-[4-(4-phenethylpiperazine-1-sulphonyl)phenyl]-1-propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2.4-dione

6-[4-(5-Benzyl-2,5-diazablcyclo[2.2.1]heptane-2-sulphonyl)-phenyl]-3-methyl-1-propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

N-[2-(Benzylmethylamino)ethyl]-4-(3-methyl-2,4dioxo-1-propyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulphonamide

N-{2-[Benzyl-(2-hydroxyethyl)amino]ethyl}-4-(3-methyl-2,4-dioxo-1-propyl-2.3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulphonamide

3-Methyl-1-propyl-6-[4-(4-pyridin-2-yl-piperazine-1-sulphonyl)phenyl]-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

N-(1-Benzylpiperidin-4-yl)-4-(3-methyl-2,4-dioxo-1-propyl-2,3,4,5-tetrahydro-1H-pyrrolo[3.2-d]pyrimidin-6-yl)benzenesulphonamide

N-[1-(4-Fuorobenzyl)-piparidin-4-yl]-4-(3-methyl-2,4-dioxo-1-propyl-2.3,4,5-tstrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulphonamide

N-[1 -(3,4Dimethoxybenzyl)piperidin-4-yq4-(3-methyl-2,4dioxo-1-propyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-olpyrimidin-6-yl)benzenesulphonamide

4-(3-Methyl-2,4-dioxo-1-propyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-dqpyrimidin-6-yl)N-(1-thiophen-2-ylmethylpiperidin-4-yl)benzenesulphonamide

5 N-(1-Benzylpiperidin-4-yl)-N-methyl-4-(3-methyl-2,4-dioxo-1-propyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-dpyrimidin-6-yl)benzenesulphonamide

4-(3-Methyl-2,4-dioxo-1-propyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-dqpyrimidin-6-yl)-N-(2-pyridin-2-yl-ethyl)benzenesulphonamide

6-[4-(4-Benzylpiperazine-1 -sulphonyl)phenyl]-7-chloro-1,3-dimethyl-1,5-1 0 dihydropyrrolo[3,2-dpyrimidine-2,4-dione

4-(1,3-Dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-dpyrimidin-ylyN-pyridin-2-ylmethylbenzenesulfonamide

4-(1,3-Dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-olpyrimidin-6-yl)N-pyridin-3-ylmethylbenzenesulfonamide

4-(1,3-Dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-dopyrimidin-6-yl)-N-pyddinX-ylmethylbenzenesulfonamide

4-(1,3-Dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-dopyrimidin-6-yl)-N-(6-methoxypyridin-3-ylmethyl)benzenesulfonamide

N-(3-Chloropyridin-4-ylmethyl)-4-(1,3-dimethyl-2,4-dioxo-23,4,5-tetrahydro-lH-20 pyrrolo[3,2-dqpyrimidin-6-yl)benzenesulfonamide

4-(1,3-Dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-olpyrimidin-6-yl)-N-methyl-N-(2-pyridin-2-ylethyl)benzenesulfonamide

4-(1,3-Dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-olpyrimidin-6-yl)-N-(2-pyridin-3-ylethyl)benzenesulfonamide

4-(1,3-Dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-dqpyrimidin-6-yl)N-(2-pyridin-4-ylethyl)benzenesulfonamide

4-(1,3-Dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-dlpyrimidin-6-yl)-N-[2-(pyridin-2-yloxy)ethygbenzenesulfonamide4-(1,3-Dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-dqpyrimidin-6-yl)-N-[2-(6-30methoxypyridin-2-yloxy)ethyqbenzenesulfonamide4-(1,3Dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-dqpyrimidin-6-yl)-N-[2-(4-methylpyridin-2-yloxy)ethyl]benzenesulfonamide

N-[2-(5-Chloropyridin-2-yloxy)ethyl]-4-(1,3-dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-dopyrimidin-6-yl)benzenesulfonamide

4-(1,3-Dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-olpyrimidin-6-yl)N-[2-C5-trifiuoromethylpyridin-2-yloxy)ethyqbenzenesulfonamide

4-(1 ,3-Dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3.2-dopyrimidin-6-yl)N-[2-(pyridin-3-yloxy)ethyl]benzenesulfonamide

5 4-(1 ,3-Dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-dlpyrimidin-6-yl)-N-[2-(pyrazin-2-yloxy)ethyl]benzenesulfonamide

4-(1 ,3-Dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-dpyrimidin-6-yl)-N-[2-(pyridin-2-ylsulfanyl)ethygIbenzenesulfonamide

4-(1 ,3-Dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-dopyrimidin-6-yl)-N-[2-1 0(pyrimidin-2-ylsulfanyl)ethyl]benzenesulfonamide

N-Benzyl-4-(1,3-dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-IH-pyrrolo[3,2-dopyrimidin-6-ylyN-[2-(pyridin-2-yloxy)ethyqbenzenesulfonamide

N-Benzyl-4-(1 ,3-dimethy1-2,4-dioxo-2,3,4,5-tetrahydro-lH-pyrrtlo[3,2-dopyrimidin--y6>N-[2-(6-methoxypyridin-2-yloxy)ethyl]benzenesulfonamide

N-Benzyl-N-[2-(6chloropyridin-3-yloxy)ethyl]-4-(1,3-dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-dqpyrimidin-6-yl)benzenesulfonarnide

6-[4-(4-Benzylpiperidine-1 -sulfonyl)phenyl]-1 ,3-dimethyl-1,5-dihydropyrrolo[3,2-dopyrimidine-2,4-dione

6-4-[4-(3-Methoxyphenyl)piperidine-1 -sulfony1]phenyi)I ,3-dimeti- ,i:-dihydropyrrolo[3,2-dopyrimidine-2,4-dione

4-(1,3-Diethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-dgpyrimidin-6-yl)-N-pyridin-2-ylmethylbenzenesulfonamide

4-(1,3-Diethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-dpyrimidin-6-yl)-N-pyridin-3-ylmethylbenzenesulfonamide

4-(1,3-Diethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-dopyrimidin-6-yl)-N-pyridin4-ylmethylbenzenesulfonamide

4-(1,3-Diethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-dqpyrimidin-6-ylyN-(6-methoxypyridin-3-ylmethyl)benzenesulfonamide

4-(1,3-Diethyl-2,4-dioxo-2,3,4,5-tetrahydro1H-pyrrolo[3,2-dqpyrimidin-6-ylyN-methyl-N-(2-30pyridin-2-ylethyl)benzenesulfonamide

4-(1,3-Diethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrroio[3,2-dgpyrimidin-6-yl)-N-(2-pyridin-3-ylethyl)benzenesulfonamide

4-(1,3-Diethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-dqpyrimidin-6-yl)-N-(2-pyridin-4-ylethyl)benzenesulfonamide

4-(I,3Diethyl-2.4-dioxo-2.3,4,5-tetrahydro-.:H-yrrolo[3,2-alpyrimidin-6yl)-N-2-(pyridin-3-yfoxy)ethybenzenesulfonamide

N-Benzyl441,3-diethyl-2,4-dioxo2,3,4,5-tetrahydro01H-pyrrolo[3,2-pyrimidin-yl)-N-2-(-din-2-ylox)ethyl benzenesuffonamide

4(2,4Dioxo1 ,3dipropyl-2,3,4,5-tetrahydro-1 H-pyrobl3,2-pyrimidin-yl)Nmethyl-N-(2-pyridin-2-ylethyl)benzenesulfonamide

4-(1-Methyl-2,dioxopropyl-2,3,4,-tetrahydro1H-pyrrolo[3,2-dlpyrimidin6-ylI-pyridin-2-ylmethylbenzenesulfonamide

4-(1-Methyl2,dioxo-3-propyl-2,3,4,5tetrahydro1H-pyrfolo[3,2-Apyrimidin-6-yl)N-10 pyridin-3-ylmethylbenzenesulfonamide

N-(6-Methoxypyridin-3ylmethyt)(1-methyl-2.4-dioxo-3-propyl2,3.4,5-tetrahydro-1H-pyrrolo[3,2-dqpyrimidinyl)benzenesulfonamide..

N-Methy+(1 -methyl-2,4 dioxo-3 propyl-2,3.45tetrahydro1H-pyrrolo[3,2-pyrimidinsyi)N-2-pyridin-2-ylethyl)benzenesulfonamide

4-(1 -Methyl-2,4-iox>opropyl 2,3,4,5tetrakhydro-1H-pyrrolo[3,2-pyrimidin-6-yl)-N(2-pyridin-3-yiethyl)benzenesulfonamide

4-(1 -Methyl-2,4diox>opropyl-2,3,4,5-tetrahydroH-pyrrolo[3.2-4pyrimidinyl)-N-(2-pyridin-4-ylethyl)benzenesulfonamide

4(1-Methyl-2,4 dioxopropyt2,3,4,5-tetrahydro1H-pyrrolo[3,2-dgpyrimidin6-yl)N-2-20(pyridin-2-yloxy)ethyl]benzenesulfonamide

N-Benzyl4-(1 -methyl-2.4-dioxo-3-propyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-aqpyrimidin4-yi)-N-[2-(pyridin-2-yloxy)ethylqbenzenesulfonamide

4(3-Methyl-2.4-dioxo1 -propyl-2,3,4,5-tetrahydroIH-pyrrolo[3,2-dqpyrimidin6-ylI-pyridin-2-ylmethylbenzenesulfonamide

4(3-Methyl-2,4-dioxo-l-propyl-2,3,4,5-tetrahydro1 H-pyrroo[3₁2-apynmidin4-yl)-pyridin-3-ylmethylbenzenesulfonamide

4-(3-Methyl-2,4-dioxo--propyl-2.3,4,5tetrahydro-H-pyrrolo[3,2-dpyrimidin-6-yl)-N-pyridinylmethylbenzenesulfonamide

N-(6-Methoxypyridin-3-yfmethyl)(3-methyl-24dioxo1-propyl-2,3,4,5-tetrahydro-1 H-30pyrrolo[3.2-cpyrimidinyl)benzenesulfonamide

N-(3-Chloropyridinylmethyl)4(3methyl-24dioxo-1-propyl-2,3,4,5tetrahydro-1H-pyrrolo[3,2-oapyrimidinyl)benzenesulfonamide

N-Methyl443-methyl2,dioxo-l-propyl2,3,4,5tetrahydro-lH-pyrrolo[3,2-dlpyrimidin-6-yi)N-(2-pyndin-2-yiethyl)benzenesulfonamide

4(3Methyl-2.4 dioxo-l-propyl-2,3,4,5tetrahydroH-pyrmolo[3.2-pyrimidin-yl)N(2-pyridin-3yl-ethyl)benzenesulfonamide

4(3Methyl-2,dioxo1-propyl2,3,4,5tetrahydro-H-pyrrolo[3,2-pyrimidin4-yl)N-(2--yridinylethyl)benzenesulfonamide

4-(3-Methyl-2-ioxo-ipropyl-2,3,4,5tetrahydro1Hpyrrolo[3,2-iApyrimidin6-yl)N42-.(pyridin-2-yloxy)-ethybenzenesulfonamide

1,3-Dimethyl-[4(2,3,5,6-tetrahydro-[1,21bipyrazinyl4sulfonyl)phenyU-1,5-*dihydropyrrolo[3,2-olpydmidine-2,4dione

4(I-Ethyl-3methyl-2,dioxo-2.34,5tetrahydro1 H-pyrrolo[3,2-dpyrimidin6yl)N-pyridin-2-ylmethylbenzenesulfonamide

41 ( -Ethyl-methyl-2,4-dioxo-2,3,4,5tetrahydro1 Hpyrrolo[3,24pyrimidin6yl)N-(2-pyridin-2-yiethyl)-benzenesulfonamide

4-(l -Et h y l--m et h y l-2 ,4dio x2,3,4,tetrahydr H-pyrroIo[3,2-d1pyrnmidin-6-yl)-N-[2-(pyridin-2-yloxy)ethyl]-benzenesulfonamide

4-(1 -Ethyl-methyl-2,4dioxo23.4, 5tetra.hydro1H-pyrrolo[3,2-d]pyrimidir4yl)N-(6-methoxy-pyridin-3ylmethyl)-benzenesulfonamide

441,3-Bis-(3-methoxypropyl-2. dioxo-2,3,4,5-tetrahydro-H-pyrrolo[3,2-dpyrimidin6-yt]-N-pyndin-3-ylmethylbenzenesulphonamide

6-44-(4Bromobenzylipiperazine-1 -sulphony1]phenyl)1,3-bis-(2-methoxyethyl)-1, -dihydropyrrolo[3,2-oapyrimidine2,4-dione

4-[1,3Bis-(2ethylsulphanylethyl)-2,4dioxo2,3,415tetrahydro-H-pyrrolo[3,2-dpyrimidin-yl]-N-pyrdinylmethylbenzenesulphonamide

6-4[4(4-Bromobenzyl)piperazine1 -sulphonyuphenyl1,3-bis-(2-methylsulphanyl-ethyl)-1,5dihydropyrrolo[3,2-dipyrimidine-2,4-dione

{4-4-(Bromobenzyl)piperazine-1 ulphonyuphenyl}3methyl-l-pyridinylmethyl-1,5-dihydro-pyrrolo[3,2-pyrimidine2,4-dione

N-MethyiZ(3-methyl-2,4dioxo1 -pyndinyllmethyl-2.3,4,5-tetrahydro1Hpyrrolo[3,2-capyrmidin-6-yi)N-(2-pyddin-2-yl-ethyl)benzenesulphonamide

6[-44-Benzylpiperazine1 -sulphonyl)phenyl]-3methyl-1-phenethyl1.5-dihydro-pyrrolo[3,2-olpyrimidine2_(,)4-dione

4(Methyl2,4dioxo-1 -phenethyl-2,3,4,5tetrahydro1H-pyrrolo[3.2-pyrimidin6-yl)N-pyridin-2-ylmethylbenzenesulphonamide

6-[4(4Benzylpiperazine- -sulphonyl)phenyq-1 ,3-bis-cyclopropylmethyl-1.5-dihydro-pyrrolo[3,2-pyrimidine-24dione

4-(1 ,3-Bis-cyclopropylmethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-ilpyrimidin-6-yl)-N-(2-pyridin-3-yl-ethyl)benzenesulphonamide

4-[2,4-Dioxo-1 ,3-bis-(2,2,2-trifluoroethyl)-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-dpyrimidin-6-yQ-N-(6-methoxypyridin-3-ylmethyl)benzenesulphonamide

6-[4-(4-Benzylpiperazine-1-sulphonyl)phenyl]-1,3-bis-(2,2,2-trifluoroethyl)-1,S-dihydro-pyrrolo[3,2-dopyrimidine-2,4-dione

N-(6-Methoxypyrdin-3-ylmethyl)-4-3-methyl-l-(2-morpholin-4-yl-ethyl)2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-dqpyrimidin6-ygbenzenesulphonamide

6-[4-(4-Benzylpiperazine-1 -sulphonyl)phenyo-3-methyl-1-(2-morpholin-4-ylethyl)1 ,5-1 0dihydropyrrolo[3,2-dopyrimidine-2,4-dione

1 -Benzyl-6*4-[4-(4-bromobenzyl)piperazine-1-sulphonyophenyl}-3-methyl-1,5-dihydropyrrolo[3,2-dapyrimidine-2,4-dione

4-(1 -Benzyl-3-methyl-2,4-dioxo-2,3,4,5tetrahydro-1H-pyrrolo[3,2-dlpyrimidin-6-yl-N-[2-(pyridin-2-yloxy)ethylgbenzenesulphonamide

3-6-[4-(4-Benzylpiperazine- 1-sulphonyl)pheny13-3-methyl-2.4-dioxo-2,3,4,5-tetrahydro-pyrrolo[3,2-dopyrimidin-1-yl)propionicacid methyl ester

4-I -(3-HydroxypropylY3-methyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-ylq-N-[2-(pyridin-2-yloxy)ethyl]benzenesulphonamide

4-(4-Benzylpiperazine-l-sulphonyl)phenyl]-1-cyclopentyl-3-methyl-1,5-- O20 dihydropyrrolo[3,2-dipyrimidine-2,4-dione

4-(1 -Cyclopentyl-3-methyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-dpyrimidin-6-yl)-N-(2-pyridin-4-yl-ethyl)benzenesulphonamide

Of outstanding interest are:

4-(1 ,3-Dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-alpyrimidin6-yl)-N-[2-(pyridin-²-yloxy)ethyqbenzenesulfonamide

4-(1 ,3-Dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-IH-pyrrolo[3,2-apyrimidin-6-yl)-N-[2-(6-methoxypyridin-2-yloxy)ethyl]benzenesulfonamide

6-[4-(4-Benzylpiperazine-1-sulphonyl)phenyl]-1,3-dimethyl-I,5-dihydropyrrolo[3,2-alpyrimidine-2,4-dione

6-4-[4-(4-Fluorobenzyl)piperazine-1 -sulphonyl]phenyl)I-methyl-3-propyl-1,5-dihydropyrrolo[3,2-dlpyrimidine-2,4-dione

6-[4-(4-Benzo[1,3]dioxol-5-ylmethylpiperazine-1 -sulphonyl)phenylo-1-methyl-3-propyl-1,5-dihydropyrrolo[3,2-dlpyrimidine-2,4-dione

6-{4-[4-(3-Fluorobenzyl)piperazine-1-sulphonyl]phenyl}-1,3-dimethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

1-Methyl-3-propyl-6-[4-(4-pyridin-2-ylpiperazine-1-sulphonyl)phenyl]-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

4(1,3-Dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-(2-pyridin-2-ylethyl)benzenesulphonamide

4-(1-Methyl-2,4-dioxo-3-propyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-(2-pyridin-2-ylethyl)benzenesulphonamide

4-(1,3-Dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-pyridin-2-ylbenzenesulphonamide

4-(1,3-Dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-(6-methoxypyridin-3-yl)benzenesulphonamide

6-{4-[4-(5-Chlorothiophen-2-ylmethyl)piperazine-1-sulphonyl]phenyl)-1,3-dimethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

6-{4-[4-(5-Chlorothiophen-2-ylmethyl)piperazine-1-sulphonyl]phenyl}-1,3-diethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

N-(1-Benzylpiperidin-4-yl)-4-(2,4-dioxo-1,3-dipropyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulphonamide

4-(1,3-Diethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-[1-(4-fluorobenzyl)piperidin-4-yl]benzenesulphonamide

According to a further feature of the present invention, the4-(pyrrolopyrimidin-6-yl)benzenesulphonamide derivatives of generalformula (I) are prepared by reaction of the corresponding sulphonylchloride of formula (II):

(wherein R¹, R² and R³ are as hereinbefore defined) and thecorresponding amine (III):

(wherein R⁴ and R⁵ are as hereinbefore defined). The reaction is carriedout in an organic solvent, preferably a polar aprotic organic solventsuch as dioxane, methylene chloride or tetrahydrofuran, at a temperaturefrom 10° C. to 40° C. and in the presence of an organic base, preferablyan amine base such as triethylamine or polymer supported morpholine. Thethus obtained 4-(pyrrolopyrimidin-6-yl)benzenesulphonamide derivative isthen isolated by standard methods known in the art.

When R³ is hydrogen, the sulphonyl chloride of formula (II) is obtainedfrom the corresponding compound of formula (IV):

(wherein R¹, R² and R³ are as hereinbefore defined), by reaction with anexcess of chlorosulphonic acid and optionally thionyl chloride,preferably under a nitrogen atmosphere and at a temperature from −5° C.to 10° C.

When R³ is a chlorine atom, the sulphonyl chloride of formula (II) isobtained from the corresponding compound of formula (IV) by reactionwith a mixture of chlorosulphonic acid and sulphuryl chloride,preferably under a nitrogen atmosphere and at a temperature from −5° C.to 10° C.

When R³ is a bromine or an iodine atom, the sulphonyl chloride offormula (II) is obtained from the corresponding sulphonyl chloride offormula (II) where R³ is a hydrogen atom by reaction with bromine oriodine monochloride in glacial acetic acid at room temperature.

Other substitutions at R³ can be introduced by - reaction of thecorresponding compounds of the general formulae (II) or (IV), or aprotected version of them, with an appropiate electrophile.

The 6-phenyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione derivativesof formula (IV) can be prepared by reaction of the corresponding6-methyl-5-nitrouracils (V):

(wherein R¹ and R² are as hereinbefore defined), and benzaldehyde (VI):

followed by reductive cyclisation of the resulting5-nitro-6-styryluracils by methods known in the art, e.g. C. E. Mller etal., J. Med. Chem. 1994, 37, 1526-1534 and references cited therein.

When the defined groups R¹ to R⁵ are susceptible to chemical reactionunder the conditions of the hereinbefore described processes or areincompatible with said processes, alternative processes can be readilycarried out utllising organic synthetic chemistry methods to, forexample, protect functional groups and finally eliminate protectinggroups.

The 4-(pyrrolopyrimidin-6-yl)benzenesulphonamide derivatives of formula(I) can be converted by methods known per se into pharmaceuticallyacceptable salts or N-oxides.

Preferred salts are acid addition salts obtainable by treatment withorganic or inorganic acids such as fumaric, tartaric, succinic orhydrochloric acid. Also 4-(pyrrolopyrimidin-6-yl)benzenesulphonamidederivatives of formula (I) in which there is the presence of an acidicgroup may be converted into pharmacologically acceptable salts byreaction with an alkali metal hydroxide or an organic base such assodium or potassium hydroxide. The acid or alkali addition salts soformed may be interchanged with suitable pharmaceutically acceptablecounter ions using processes known per se.

Adenosine 2B Receptor Subtype Competition Radioligand Binding

Human membranes from recombinant A_(2B) receptors were purchased fromReceptor Biology, Inc.(USA).

Competition assays were carried out by incubation of membranes fromhA_(2B) receptors transfected to HEK293 cells, [³H]DPCPX as radioligand,buffer (50 mM Tris-HCl (pH 6.5), 10 mM MgCl₂, 1 mM EDTA, 0.1 mMbenzamidine, 2units/ml adenosine deaminase), and unlabelled ligand in atotal volume of 0.1 ml for 30 min at 25° C. NECA was used to determinatenon-specific binding. Filter over Schleicher&Schuell GF/52 filters(pre-soaked 0.5% polyethylenyimine) in a Brandel cell harvester. Unboundradioligand was removed with 4×2 ml ice-cold 50 mM Tris-Hcl (pH 6.5).

Adenosine 2A Receptor Subtype Competition Radioligand Binding

Human membranes from recombinant A_(2A) receptors were purchased fromReceptor Biology, Inc.(USA).

Competition assays were carried out by incubation of membranes fromhA_(2A) receptors transfected to HEK293 cells, [³H]ZM241385 asradioligand, buffer (50 mM Tris-HCl (pH 7.4), 1 mM MgCl₂, 1 mM EDTA,2units/ml adenosine deaminase), and unlabelled ligand in a total volumeof 0.2 ml for 90 min at 25° C. NECA was used to determinate non-specificbinding. Filter over Schleicher&Schuell GF/52 filters (pre-soaked 0.5%polyethylenyimine) in a Brandel cell harvester. Unbound radioligand wasremoved with 3×3 ml ice-cold 50 mM Tris-Hcl 50 (pH 7.4), 0.9% NaCl.

The results are shown in Table 1 and Table 2. TABLE 1 Example IC₅₀A_(2B) (nM) 172 17 173 5 1 16 107 9 118 6 3 7 126 12 37 14 132 17 38 1236 18 18 4

It can be seen from Table 1 that the compounds of formula (I) are potentinhibitors of the A_(2B) adensosine receptor subtype. Preferred4-(pyrrolopyrimidin-6-yl)benzenesulphonamide derivatives of theinvention possess an IC₅₀ value for the inhibition of A_(2B) (determinedas defined above) of less than 50 nM, preferably less than 20 nM andmost preferably less than 10 nM. TABLE 2 Example IC₅₀ A_(2A) (nM) 18 8559 28 38 75 97 60 69 84

It can be seen from Table 2 that the compounds of formula (I) are potentinhibitors of the A_(2A) adenosine receptor subtype. Some preferred4-(pyrrolopyrimidin-6-yl)benzenesulphonamide derivatives of theinvention possess an IC₅₀ value for the inhibition of A_(2A) (determinedas defined above) of less than 100 nM and most preferably less than 50nM.

The 4-(pyrrolopyrimidin-6-yl)benzenesulphonamide derivatives of theinvention are useful in the treatment or prevention of diseases known tobe susceptible to improvement by treatment with an antagonist of A_(2A)and/or A_(2B) adenosine receptors. For example (see WO 01/16134, WO01/02400, WO 01/80893 or WO 00/73307), Parkinson's disease, Alzheimer'sdisease, Huntington chorea, Wilson's disease, asthma,bronchoconstriction. allergic diseases. inflammation, reperfusioninjury, myocardial ischemia, atherosclerosis, hypertension, retinopathy,diabetes mellitus, inflammation, gastrointestinal tract disorders,and/or autoimmune diseases. Examples of autoimmune diseases which can betreated or prevented using the compounds of the invention are Addison'sdisease, autoimmune hemolytic anemia, Crohn's disease, Goodpasture'ssyndrome, Graves disease, Hashimoto's thyrolditis, idiopathicthrombocytopenic purpura, insulin-dependent diabetes mellitus, multiplesclerosis, myasthenia gravis, pemphigus vulgaris, pernicious anemia,poststreptococcal glomerulonephritis, psoriasis, rheumatoid arthritis,scleroderma, Sjogren's syndrome, spontaneous infertility, and systemiclupus erythematosus.

Accordingly, the 4-(pyrrolopyrimidinyl)benzenesulphonamide derivativesof the invention and pharmaceutically acceptable salts thereof, andpharmaceutical compositions comprising such compound and/or saltsthereof, may be used in a method of treatment of disorders of the humanbody which comprises administering to a subject requiring such treatmentan effective amount of a 4-(pyrrolopyrimidin-6-yl)benzenesulphonamidederivative of the invention or a pharmaceutically acceptable saltthereof.

The present invention also provides pharmaceutical compositions whichcomprise, as an active ingredient, at least a4-(pyrrolopyrimidin6-yl)benzenesulphonamide derivative of formula (I) ora pharmaceutically acceptable salt thereof in association with apharmaceutically acceptable excipient such as a carrier or diluent. Theactive ingredient may comprise 0.001% to 99% by weight, preferably 0.01%to 90% by weight of the composition depending upon the nature of theformulation and whether further dilution is to be made prior toapplication. Preferably the compositions are made up in a form suitablefor oral, topical, nasal, rectal, percutaneous or injectableadministration.

The pharmaceutically acceptable excipients which are admixed with theactive compound, or salts of such compound, to form the compositions ofthis invention are well-known per se and the actual excipients useddepend inter alia on the intended method of administering thecompositions.

Compositions of this invention are preferably adapted for injectable andper os administration. In this case, the compositions for oraladministration may take the form of tablets, retard tablets, sublingualtablets, capsules, inhalation aerosols, inhalation solutions, dry powderinhalation, or liquid preparations, such as mixtures, elixirs, syrups orsuspensions, all containing the compound of the invention; suchpreparations may be made by methods well-known in the art.

The diluents which may be used in the preparation of the compositionsinclude those liquid and solid diluents which are compatible with theactive ingredient, together with colouring or flavouring agents, ifdesired. Tablets or capsules may conveniently contain between 2 and 500mg of active ingredient or the equivalent amount of a salt thereof.

The liquid composition adapted for oral use may be in the form ofsolutions or suspensions. The solutions may be aqueous solutions of asoluble salt or other derivative of the active compound in associationwith, for example, sucrose to form a syrup. The suspensions may comprisean insoluble active compound of the invention or a pharmaceuticallyacceptable salt thereof in association with water, together with asuspending agent or flavouring agent.

Compositions for parenteral injection may be prepared from solublesalts, which may or may not be freeze-dried and which may be dissolvedin pyrogen free aqueous media or other appropriate parenteral injectionfluid.

Effective doses are normally in the range of 2-2000 mg of activeingredient per day. Daily dosage may be administered in one or moretreatments, preferably from 1 to 4 treatments, per day.

The syntheses of the compounds of the invention and of the intermediatesfor use therein are illustrated by the following Examples (includingPreparation Examples (Preparations 1-12)) which do not limit the scopeof the invention in any way. ¹H Nuclear Magnetic Resonance Spectra wererecorded on a Varian Gemini 300 spectrometer. Melting points wererecorded using a Perkin Elmer DSC-7 apparatus. The chromatographicseparations were obtained using a Waters 2690 system equipped with aSymmetry C18 (2.1×10 mm, 3.5 μM) column. As detectors a Micromass ZMDmass spectrometer using ES ionization and a Waters 996 Diode Arraydetector were used. The mobile phase was formic acid (0.46 ml), ammonia(0.115 ml) and water (1000 ml) (A) and formic acid (0.4 ml), ammonia(0.1 ml), methanol (500 ml) and acetonitrile (500 ml) (B): initiallyfrom 0% to 95% of B in 20 min. and then 4 min. with 95% of B. Thereequilibration time between twNo injections was 5 min. The flow ratewas 0.4 ml/min. The injection volume was 5 μl. Diode array chromatogramswere processed at 210 nm.

PREPARATION EXAMPLES Preparation 14-(1,3-Dimethyl-2,4-dioxo-2,3,4,5tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-benzenesulphonylchloride

a) A mixture of 1,3,6-trimethyl-5-nitro-1H-pyrimidine-2,4dione (3.00 g,15.06 mmol), benzaldehyde (1.58 ml, 15.56 mmol), piperidine (1.41 ml,15.56 mmol) and a 3A molecular sieve (6.00 g) in ethanol (70 ml) wasrefluxed for 4 hours, filtered and the solid was treated with a mixtureof chloroform and methanol. The resulting suspension was filtered againand the filtrates were evaporated. The residue was triturated withdiethyl ether and the precipitate collected by filtration and driedunder vacuum to yield1,3-dimethyl-5-nitro-6-((E)styryl)-1H-pyrimidine-2,4dione (2.61 g, 60%)as a yellow solid.

b) To a stirred solution of the above compound (2.61 g, 9.08 mmol) informic acid (80 ml) was slowly added sodium dithionite (9.30 g, 45.42mmol) and the mixture was refluxed overnight. The resulting mixture wascooled to room temperature and it was poured into water. The precipitatewas collected by filtration, washed with water and dichloromethane andthen dried under vacuum to yield1,3dimethyl-6-phenyl-1,5-dihydropyrrolo[3,2-d]pyrimidine2,4-dione (1.54g, 66%) as a white solid.

c) The above compound (500 mg, 1.96 mmol) was added portionwise to amixture of chlorosulphonic acid (2.5 ml) and thionyl chloride (0.25 ml)and stirred at 0° C. for 1 hour and then at room temperature for 1 h 30min. The reaction mixture was carefully poured into stirred ice-waterand the resulting precipitate was collected by filtration, washed withwater and diethyl ether and then dried under vacuum to yield the titleproduct (607 mg, 88%) as a yellow solid.

¹H-NMR δ(DMSO): 12.5 (s, 1H), 7.9 (d, 2H), 7.6 (d, 2H), 6.8 (s, 1H), 3.5(s, 3H), 3.3 (s, 3H).

Preparation 24-(1,3-Diethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulphonylchloride

Obtained as a yellow solid (29% overall) from1,3-diethyl-6-methyl-5-nitro-1H-pyrimidine-2,4-dione following theprocedure described in Preparation 1.

¹H-NMR δ(DMSO): 12.4 (s, 1H), 7.9 (d, 2H), 7.8 (d, 2H), 6.8 (s, 1H), 3.9(m, 4H), 1.2 (dt, 6H).

Preparation 34-(2,4-Dioxo-1,3-dipropyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulphonylchloride

Obtained as a yellow solid (18% overall) from6-methyl-5-nitro-1,3-diprbpyl-1H-pyrimidine-2,4-dione following theprocedure described in Preparation 1.

¹H-NMR δ(DMSO): 12.2 (s, 1H), 7.9 (d, 2H), 7.6 (d, 2H), 6.8 (s, 1H), 3.9(m, 4H), 1.6 (m, 4H), 0.9 (m, 6H).

Preparation 44-(1-Methyl-2,4-dioxo-3-propyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulphonylchloride

Obtained as a yellow solid (50% overall) from1,6-dimethyl-5-nitro-3-propyl-1H-pyrimidine-2,4-dione following theprocedure described in Preparation 1.

¹H-NMR δ(DMSO): 12.4 (s, 1H), 7.9 (d, 2H), 7.6 (d, 2H), 6.65 (s, 1H),3.9 (t, 2H), 3.4 (s, 3H), 1.6 (m, 2H), 0.9 (t, 3H).

Preparation 54-(3Methyl-2,4-dioxo-1-propyl-2,3,4,5tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulphonylchloride

Obtained as a yellow solid (40% overall) from3,6-dimethyl-5-nitro-1-propyl-1H-pyrimidine-2,4-dione following theprocedure described in Preparation 1.

¹H-NMR δ(DMSO): 12.4 (s, 1H), 7.9 (d, 2H), 7.6 (d, 2H), 5.8 (s,1H), 3.85(t, 2H), 3.35 (s, 3H), 1.7 (m, 2H), 0.9 (t, 3H).

Preparation 6

4-(7-Chloro-1,3-dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulphonylchloride

The title compound of Preparation 1 (600 mg,1.69 mmol) was suspended inglacial acetic acid (6 ml), sulphuryl chloride was added dropwise (205μl, 2.54 mmol) and the mixture was stirred at room temperature for 3hours. The reaction mixture was then filtered, washed with dietyhl etherand dried to yield the title product as a yellow solid (384 mg, 58%).

¹H-NMR δ(DMSO): 12.9 (s, 1H), 7.6 (m, 4H), 3.7 (s, 3H), 3.2 (s, 3H).

EXAMPLES

TABLE 3 (I)

Compounds of formula (I) wherein R³ = H: R¹R² R¹ = Me R¹ = Et R¹ = nProR¹ = nPro R¹ = Me R² = Me R² = Et R² = nPro R² = Me R² = nPro NR⁴R⁵  143 76 106 133

 2 44 77 107 134

 3 45 78 108 135

 4 46 79 109 —

 5 — — — —

 6 47 80 110 136

 7 48 81 111 137

 8 49 82 112 138

 9 50 83 113 139

 10 51 84 114 140

 11 52 85 115 141

 12 53 86 116 142

 13 54 87 117 143

 14 55 88 118 144

 15 56 89 119 145

 16 57 — 120 —

 17 58 90 121 146

 18 59 91 122 147

 19 60 92 123 148

 20 61 93 — 149

 21 — — — 150

 22 62 94 124 151

— 63 95 — 152

 23 — — — —

 24 64 — — 153

 25 — — — —

 26 65 — 125 154

— 66 — — 155

 27 67 96 126 156

 28 — — — —

 29 68 97 127 157

 30 69 98 128 158

 31 70 99 129 159

 32 71 100  130 160

 33 72 101  131 161

 34 73 102  — —

 35 74 — — —

 36 — 103  — —

 37 75 104  132 162

 38 — 105  — —

 39 — — — —

 40 — — — —

 41 — — — —

 42 — — — —

164 186  — 196 204

165 187  — 197 205

166 188  — — 206

167 189  — 198 207

168 — — 208

169 190  195  199 209

170 191  — 200 210

171 192  — 201 211

172 193  — 202 212

173 — — — —

174 — — — —

175 — — — —

176 — — — —

177 — — — —

178 — — — —

179 — — — —

180 — — — —

181 194  — −203

182 — — — —

183 — — — —

184 — — — —

185 — — — —

Compounds of formula (I) wherein R³ = Cl: 163 — — — —

Example 1

6-[4-(4-Benzylpiperazine-1-sulphonyl)phenyl]-1,3-dimethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione

To a mixture of the title compound of Preparation 1 (0.1 g, 0.28 mmol)and triethylamine (0.043 ml, 0.31 mmol) in dichloromethane (5 ml) wasadded 1-benzylpiperazine (0.054 ml, 0.31 mmol) and the resulting mixturewas stirred at room temperature overnight. The reaction mixture wasdiluted with dichloromethene, washed with an aqueous solution of sodiumbicarbonate in water, dried (MgSO₄) and evaporated under reducedpressure. The resulting crude residue was triturated with diethyletherand the precipitate collected by filtration and dried under vacuum toyield the title compound (65 mg, 47%). ESI/MS m/e: 494 ([M+H]⁺,C₂₅H₂₇N₅O₄S)

Retention Time (min.): 6.6

Examples 2-42 and 164-185

These compounds were synthesized from the title compound of Preparation1 following the procedure of example 1 and using the correspondingreactant. The ESI/MS data, HPLC retention times and yields aresummarised in Table 4. TABLE 4 ESI/MS m/e Retention Example MolecularFormula [M + H]⁺ Time (min.) Yield % 2 C₂₅H₂₆FN₅O₄S 512 6.5 52 3C₂₅H₂₆FN₅O₄S 512 7.2 35 4 C₂₅H₂₅F₂N₅O₄S 530 7.5 44 5 C₂₅H₂₆FN₅O₄S 5126.9 85 6 C₂₅H₂₆ClN₅O₄S 528 7.4 70 7 C₂₅H₂₆ClN₅O₄S 528 7.9 70 8C₂₅H₂₆BrN₅O₄S 572 7.7 50 9 C₂₅H₂₆BrN₅O₄S 573 8.8 56 10 C₂₆H₂₆F₃N₅O₄S 5628.6 74 11 C₂₉H₃₅N₅O₄S 550 8.0 35 12 C₂₆H₂₉N₅O₅S 524 5.9 65 13C₂₆H₂₉N₅O₅S 524 6.3 62 14 C₂₆H₂₇N₅O₆S 538 6.5 58 15 C₂₆H₂₆N₆O₄S 519 7.258 16 C₂₃H₂₅N₅O₅S 484 5.5 29 17 C₂₃H₂₅N₅O₄S₂ 500 6.6 80 18C₂₃H₂₄ClN₅O₄S₂ 535 8.9 84 19 C₂₄H₂₆N₆O₄S 495 5.8 26 20 C₂₆H₂₉N₅O₄S 5086.2 50 21 C₂₆H₂₉N₅O₄S 508 5.8 54 22 C₂₆H₂₈FN₅O₄S 526 6.3 59 23C₂₇H₂₉N₅O₄S 520 6.5 58 24 C₂₆H₂₇N₅O₄S 506 5.6 64 25 C₃₁H₃₁N₅O₄S 570 10.766 26 C₂₄H₂₇N₅O₄S 482 5.9 62 27 C₂₃H₂₄N₆O₄S 481 7.1 58 28 C₂₃H₂₅N₇O₅S512 6.6 63 29 C₂₆H₂₉N₅O₄S 508 5.8 44 30 C₂₆H₂₈FN₅O₄S 526 5.9 60 31C₂₈H₃₃N₅O₆S 566 5.4 49 32 C₂₄H₂₇N₅O₄S₂ 514 5.3 54 33 C₂₇H₃₁N₅O₄S 522 6.047 34 C₂₅H₂₇N₅O₄S 494 5.5 72 35 C₂₆H₂₉N₅O₄S 508 5.7 74 36 C₂₀H₁₉N₅O₅S442 8.0 84 37 C₂₁H₂₁N₅O₄S 440 5.5 54 38 C₁₉H₁₇N₅O₄S 412 6.6 52 39C₂₀H₁₉N₅O₄S 526 6.4 24 40 C₂₄H₂₅N₅O₄S 480 9.4 81 41 C₂₅H₂₄F₃N₅O₄S 54810.2 26 42 C₂₃H₂₂Cl₂N₆O₄S 550 9.5 48 164 C₂₀H₁₉N₅O₄S 426 6.4 45 165C₂₀H₁₉N₅O₄S 426 5.7 82 166 C₂₀H₁₉N₅O₄S 426 5.3 44 167 C₂₁H₂₁N₅O₅S 4567.2 52 168 C₂₀H₁₈ClN₅O₄S 461 7.3 25 169 C₂₂H₂₃N₅O₄S 455 6.0 15 170C₂₁H₂₁N₅O₄S 440 5.4 58 171 C₂₁H₂₁N₅O₄S 440 5.1 65 172 C₂₁H₂₁N₅O₅S 4567.3 66 173 C₂₂H₂₃N₅O₆S 487 8.1 89 174 C₂₂H₂₃N₅O₅S 471 7.6 90 175C₂₁H₂₀ClN₅O₅S 491 8.3 91 176 C₂₂H₂₀F₃N₅O₅S 524 8.5 65 177 C₂₁H₂₁N₅O₅S456 5.8 85 178 C₂₀H₂₀N₆O₅S 457 6.9 68 179 C₂₁H₂₁N₅O₄S₂ 473 7.8 75 180C₂₀H₂₀N₆O₄S₂ 474 7.1 65 181 C₂₈H₂₇N₅O₅S 547 9.3 44 182 C₂₉H₂₉N₅O₆S 57710.1 74 183 C₂₈H₂₆ClN₅O₅S 581 9.4 74 184 C₂₆H₂₈N₄O₄S 494 9.8 54 185C₂₆H₂₈N₄O₅S 510 9.3 49

Example 172) δ ¹H NMR (DMSO): 12.65 (bs, 1H), 8.18 (d, 2H), 7.95 (t,1H), 7.82 (d, 2H), 7.66 (dd, 1H), 6.98 (t, 1H), 6.9 (s, 1H), 6.75 (d, 1H), 4.22 (t, 2H), 3.43 (s, 3H), 3.25 (s, 3H), 3.21 (q, 2H.

(Example 173) δ ¹H NMR (DMSO): 8.05 (d, 2H), 7.85 (d, 2H), 7.50 (t, 1H),6.90 (s, 1H), 6.5 (m, 2H), 3.80 (s, 3H), 3.45 (s, 3H), 3.35 (m, 2H),3.15 (s, 3H), 3.05 (s, 3H).

Examples 43-75 and 186-194

These compounds were synthesized from the title oompound of Preparation2 following the procedure of example 1 and using the correspondingreactant. The ESI/MS data, HPLC retention times and yields aresummrarised in Table 5. TABLE 5 ESI/MS m/e Retention Example MolecularFormula [M + H]⁺ Time (min.) Yield % 43 C₂₇H₃₁N₅O₄S 522 7.1 20 44C₂₇H₃₀FN₅O₄S 540 7.5 70 45 C₂₇H₃₀FN₅O₄S 540 8.3 62 46 C₂₇H₂₉F₂N₅O₄S 5588.6 65 47 C₂₇H₃₀ClN₅O₄S 556 8.6 48 48 C₂₇H₃₀ClN₅O₄S 556 9.1 77 49C₂₇H₃₀BrN₅O₄S 601 8.9 76 50 C₂₇H₃₀BrN₅O₄S 601 9.9 63 51 C₂₈H₃₀F₃N₅O₄S590 9.6 60 52 C₃₁H₃₉N₅O₄S 578 8.9 58 53 C₂₈H₃₃N₅O₅S 552 6.7 70 54C₂₈H₃₃N₅O₅S 552 7.2 36 55 C₂₈H₃₁N₅O₆S 566 6.9 44 56 C₂₈H₃₀N₆O₄S 547 8.350 57 C₂₅H₂₉N₅O₅S 512 6.3 50 58 C₂₅H₂₉N₅O₄S₂ 528 7.7 66 59C₂₅H₂₈ClN₅O₄S₂ 562 9.8 74 60 C₂₆H₃₀N₆O₄S 523 6.7 39 61 C₂₈H₃₃N₅O₄S 5367.0 28 62 C₂₈H₃₂N₅O₄S 554 6.6 80 63 C₂₈H₃₃N₅O₄S 536 6.8 62 64C₂₈H₃₁N₅O₄S 534 6.2 57 65 C₂₆H₃₁N₅O₄S 510 6.2 47 66 C₂₇H₃₃N₅O₅S 540 6.260 67 C₂₅H₂₈N₆O₄S 509 7.8 56 68 C₂₈H₃₃N₅O₄S 536 6.1 70 69 C₂₈H₃₂FN₅O₄S554 6.2 63 70 C₃₀H₃₇N₅O₆S 596 6.0 51 71 C₂₆H₃₁N₅O₄S₂ 542 6.0 74 72C₂₉H₃₅N₅O₄S 550 6.3 38 73 C₂₇H₃₁N₅O₄S 522 6.0 32 74 C₂₈H₃₃N₅O₄S 536 6.387 75 C₂₃H₂₅N₅O₄S 468 6.5 36 186 C₂₂H₂₃N₅O₄S 455 7.4 54 187 C₂₂H₂₃N₅O₄S455 6.7 86 188 C₂₂H₂₃N₅O₄S 455 6.2 85 189 C₂₃H₂₅N₅O₅S 485 8.1 75 190C₂₄H₂₇N₅O₄S 483 7.0 74 191 C₂₃H₂₅N₅O₄S 469 6.3 61 192 C₂₃H₂₅N₅O₄S 4696.0 80 193 C₂₃H₂₅N₅O₅S 485 8.2 58 194 C₃₀H₃₁N₅O₅S 575 9.9 65

Examples 76-105 and 195

These compounds were synthesized from the title compound of Preparation3 following the procedure of example 1 and using the correspondingreactant. The ESI/MS data, HPLC retention times and yields aresummarised in Table 6. TABLE 6 ESI/MS m/e Retention Example MolecularFormula [M + H]⁺ Time (min.) Yield % 76 C₂₉H₃₅N₅O₄S 550 8.4 60 77C₂₉H₃₄FN₅O₄S 568 8.7 74 78 C₂₉H₃₄FN₅O₄S 568 9.5 90 79 C₂₉H₃₃F₂N₅O₄S 5869.7 58 80 C₂₉H₃₄ClN₅O₄S 586 9.9 57 81 C₂₉H₃₄ClN₅O₄S 585 10.2 39 82C₂₉H₃₄BrN₅O₄S 629 10.1 58 83 C₂₉H₃₄BrN₅O₄S 629 10.8 64 84 C₃₀H₃₄F₃N₅O₄S618 10.5 68 85 C₃₃H₄₃N₅O₄S 606 10.1 75 86 C₃₀H₃₇N₅O₅S 580 7.7 49 87C₃₀H₃₇N₅O₅S 580 8.4 31 88 C₃₀H₃₅N₅O₆S 594 7.9 54 89 C₃₀H₃₄N₆O₄S 575 9.452 90 C₂₇H₃₃N₅O₄S₂ 556 9.0 61 91 C₂₇H₃₂ClN₅O₄S₂ 592 10.6 25 92C₂₈H₃₄N₆O₄S 551 7.9 74 93 C₃₀H₃₇N₅O₄S 564 8.2 52 94 C₃₀H₃₆FN₅O₄S 582 7.470 95 C₃₀H₃₇N₅O₄S 564 7.8 69 96 C₂₇H₃₂N₆O₄S 537 9.0 33 97 C₃₀H₃₇N₅O₄S564 6.9 30 98 C₃₀H₃₆FN₅O₄S 582 6.9 55 99 C₃₂H₄₁N₅O₆S 624 6.8 80 100C₂₈H₃₅N₅O₄S₂ 570 6.7 77 101 C₃₁H₃₉N₅O₄S 578 7.1 29 102 C₂₉H₃₅N₅O₄S 5506.8 38 103 C₂₄H₂₇N₅O₅S 498 9.2 49 104 C₂₅H₂₉N₅O₄S 496 7.8 54 105C₂₃H₂₅N₅O₄S 468 8.1 66 195 C₂₆H₃₁N₅O₄S 511 8.4 71

Examples 106-132 and 196-203

These compounds were synthesized from the title compound of Preparation4 following the procedure of example 1 and using the correspondingreactant. The ESI/MS data, HPLC retention times and yields aresummarised in Table 7. TABLE 7 ESI/MS m/e Retention Example MolecularFormula [M + H]⁺ Time (min.) Yield % 106 C₂₇H₃₁N₅O₄S 522 7.2 70 107C₂₇H₃₀FN₅O₄S 540 7.6 66 108 C₂₇H₃₀FN₅O₄S 540 8.2 29 109 C₂₇H₂₉F₂N₅O₄S558 8.5 27 110 C₂₇H₃₀ClN₅O₄S 557 8.6 35 111 C₂₇H₃₀ClN₅O₄S 556 9.2 57 112C₂₇H₃₀BrN₅O₄S 601 8.9 84 113 C₂₇H₃₀BrN₅O₄S 601 9.9 48 114 C₂₈H₃₀F₃N₅O₄S590 9.6 41 115 C₃₁H₃₉N₅O₄S 578 8.9 32 116 C₂₈H₃₃N₅O₅S 552 6.7 58 117C₂₈H₃₃N₅O₅S 552 7.3 51 118 C₂₈H₃₁N₅O₆S 566 6.9 55 119 C₂₈H₃₀N₆O₄S 5478.3 64 120 C₂₅H₂₉N₅O₅S 512 6.3 35 121 C₂₅H₂₉N₅O₄S₂ 528 7.7 48 122C₂₅H₂₈ClN₅O₄S₂ 563 9.8 54 123 C₂₆H₃₀N₆O₄S 523 6.7 59 124 C₂₈H₃₂FN₅O₄S554 6.6 65 125 C₂₆H₃₁N₅O₄S 510 6.3 80 126 C₂₅H₂₈N₆O₄S 509 7.8 47 127C₂₈H₃₃N₅O₄S 536 6.1 81 128 C₂₈H₃₂FN₅O₄S 554 6.3 56 129 C₃₀H₃₇N₅O₆S 5966.1 63 130 C₂₆H₃₁N₅O₄S₂ 542 6.1 65 131 C₂₉H₃₅N₅O₄S 550 6.4 68 132C₂₃H₂₅N₅O₄S 468 6.6 64 196 C₂₂H₂₃N₅O₄S 455 7.4 85 197 C₂₂H₂₃N₅O₄S 4556.8 84 198 C₂₃H₂₅N₅O₅S 485 8.1 66 199 C₂₄H₂₇N₅O₄S 483 7.1 91 200C₂₃H₂₅N₅O₄S 469 6.4 45 201 C₂₃H₂₅N₅O₄S 469 6.0 30 202 C₂₃H₂₅N₅O₅S 4858.2 57 203 C₃₀H₃₁N₅O₅S 575 10.0 66

Examples 133-162 and 204-212

These compounds were synthesized from the title compound of Preparation5 following the procedure of example 1 and using the correspondingreactant. The ESI/MS data, HPLC retention times and yields aresummarised in Table 8. TABLE 8 ESI/MS m/e Retention Example MolecularFormula [M + H]⁺ Time (min.) Yield % 133 C₂₇H₃₁N₅O₄S 522 7.3 45 134C₂₇H₃₀FN₅O₄S 540 7.5 49 135 C₂₇H₃₀FN₅O₄S 540 8.5 58 136 C₂₇H₃₀ClN₅O₄S556 8.8 84 137 C₂₇H₃₀ClN₅O₄S 556 9.3 29 138 C₂₇H₃₀BrN₅O₄S 601 9.0 28 139C₂₇H₃₀BrN₅O₄S 601 10.0 56 140 C₂₈H₃₀F₃N₅O₄S 590 9.7 45 141 C₃₁H₃₉N₅O₄S578 9.1 54 142 C₂₆H₃₃N₅O₅S 552 6.8 48 143 C₂₈H₃₃N₅O₅S 552 7.4 50 144C₂₈H₃₁N₅O₆S 566 7.1 72 145 C₂₈H₃₀N₆O₄S 547 8.4 77 146 C₂₅H₂₉N₅O₄S₂ 5287.8 66 147 C₂₅H₂₈ClN₅O₄S₂ 562 9.8 36 148 C₂₆H₃₀N₆O₄S 523 6.8 39 149C₂₈H₃₃N₅O₄S 536 7.1 47 150 C₂₈H₃₃N₅O₄S 536 6.5 78 151 C₂₈H₃₂FN₅O₄S 5546.7 59 152 C₂₈H₃₃N₅O₄S 536 6.9 66 153 C₂₈H₃₁N₅O₄S 534 6.3 60 154C₂₈H₃₁N₅O₄S 510 6.3 69 155 C₂₇H₃₃N₅O₅S 540 6.3 49 156 C₂₅H₂₈N₈O₄S 5097.8 75 157 C₂₈H₃₃N₅O₄S 536 6.2 38 158 C₂₈H₃₂FN₅O₄S 554 6.2 24 159C₃₀H₃₇N₅O₆S 596 6.0 62 160 C₂₈H₃₁N₅O₄S₂ 542 6.0 50 161 C₂₉H₃₅N₅O₄S 5506.4 47 162 C₂₃H₂₅N₅O₄S 468 6.6 58 204 C₂₂H₂₃N₅O₄S 455 7.5 45 205C₂₂H₂₃N₅O₄S 455 6.9 58 206 C₂₂H₂₃N₅O₄S 455 6.4 91 207 C₂₃H₂₅N₅O₅S 4858.2 75 208 C₂₂H₂₂ClN₅O₄S 489 8.2 71 209 C₂₄H₂₇N₅O₄S 483 7.2 84 210C₂₃H₂₅N₅O₄S 469 6.4 58 211 C₂₃H₂₅N₅O₄S 469 6.0 66 212 C₂₃H₂₅N₅O₅S 4858.3 62

Example 163

This compound was synthesized from the title compound of Preparation 6and from 1-benzylpiperazine following the procedure of example 1.

ESI/MS m/e: 529 ([M+H]⁺, C₂₅H₂₆CIN₅O₄S)

Retention Time (min.): 7.4

The following examples illustrate pharmaceutical compositions accordingto the present invention and procedure for their preparation.

Composition Example 1

50,000 capsules each containing 100 mg of3-methyl-6-[5-(4-methylpiperazine-1-sulphonyl)-2-propoxyphenyl]-1-propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione(active ingredient) were prepared according to the followingformulation: Active ingredient 5 Kg Lactose monohydrate 10 Kg Colloidalsilicon dioxide 0.1 Kg Corn starch 1 Kg Magnesium stearate 0.2 Kg

Procedure

The above ingredients were sieved through a 60 mesh sieve, and wereloaded into a suitable mixer and filled into 50,000 gelatine capsules.

Composition Example 2

50,000 tablets each containing 50 mg of6-[5-(ethylpiperazine-1-sulphonyl)-2-propoxyphenyl]-3-methyl-1-propyl-1,5-dihydropyrrolo[3,2-pyrimidine-2,4dione(active ingredient) were prepared from the following formulation: Activeingredient 2.5 Kg Microcrystalline cellulose 1.95 Kg Spray dried lactose9.95 Kg Carboxymethyl starch 0.4 Kg Sodium stearyl fumarate 0.1 KgColloidal silicon dioxide 0.1 Kg

Procedure

All the powders were passed through a screen with an aperture of 0.6 mm,then mixed in a suitable mixer for 20 minutes and compressed into 300 mgtablets using 9 mm disc. and flat bevelled punches. The disintegrationtime of the tablets was about 3 minutes.

1. A compound of formula (I)

wherein R¹ and R² each independently represents: a) a hydrogen atom; b)a hydrocarbon chain chosen from an alkyl, alkenyl and alkynyl groups,wherein said hydrocarbon chain is optionally substituted by one or moresubstituents chosen from halogen, hydroxy, alkoxy, alkylthio, amino,monoalkylamino, dialkylamino, cyano, oxo, hydroxycarbonyl,alkoxycarbonyl, acylamino, carbamoyl, alkylcarbamoyl,dihydroxyphosphoryloxy and dialkoxyphosphoryloxy groups; or c) a groupof formula—(CH₂)_(n)-R⁶ n is an integer from 0 to 4 and R⁶ represents a 3- to7-membered aromatic or non-aromatic cyclic group containing from 0 to 4heteroatoms chosen from N, O and S, wherein said 3- to 7-memberedaromatic or non-aromatic cyclic group is optionally bridged and/or fusedto another 3- to 7-membered aromatic or non- aromatic cyclic groupcontaining from 0 to 4 heteroatoms chosen from N, O and S; and whereineach of the cyclic groups in the moiety R⁶ being is independentlyoptionally substituted by one or more R⁷ substituents. R⁷ represents agroup chosen from halogen, alkyl, alkenyl, alkynyl, aryl, arylalkyl,cycloalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, hydroxy,alkylenedioxy, alkoxy, alkylthio, amino, monoalkylamino, dialkylamino,nitro, cyano, oxo, hydroxycarbonyl, alkoxycarbonyl, acylamino,carbamoyl, alkylcarbamoyl, dihydroxyphosphoryloxy anddialkoxyphosphoryloxy groups; wherein each of the hydrocarbon chains andeach of the cyclic moieties in R⁷ is independently optionallysubstituted by one or more further R⁸ substituents, R⁸ represents agroup chosen from halogen, hydroxy, oxo, cyano, alkyl, difluoromethyl,trifluoromethyl, alkoxy, alkylenedioxy, alkylthio, acylamino, carbamoyl,alkylcarbamoyl, dihydroxyphosphoryloxy, dialkoxyphosphoryloxy,hydroxyalkoxy, phenyl, alkoxycarbonyl, amino, monoalkylamino,dialkylamino and hydroxycarbonyl groups; R³ represents a hydrogen orhalogen atom, or a nitro, alkoxycarbonyl or alkyl group; wherein thealkyl group is optionally substituted by one or more substituents chosenfrom hydroxy, alkoxy, alkylthio, amino, monoalkylamino, dialkylamino,hydroxycarbonyl, alkoxycarbonyl, acylamino, carbamoyl sandalkylcarbamoyl groups; R⁴ and R⁵ are the same or different, eachindependently representing: a) hydrogen; b) a group of formula—(CH₂)_(n)-R⁶; c) or a hydrocarbon chain chosen from alkyl, alkenyl andalkynyl, wherein said hydrocarbon chain whiGh is optionally substitutedby one or more substituents chosen from —(CH₂)_(n)-R⁶, —O—(CH₂)_(n)-R⁶,—S—(CH₂)_(n)-R⁶, —NH—(CH₂)_(n)-R⁶, hydroxy, oxo, halogen, alkoxy,alkylthio, amino, monoalkylamino, and dialkylamino groups; wherein eachof the alkyl chains in the alkoxy, alkylthio, monoalkylamino ordialkylamino substituents is independently optionally substituted by oneor more further substituents chosen from —(CH₂)_(n)-R⁶, hydroxy, oxo,halogen, alkoxy, alkylthio, amino, monoalkylamino and dialkylaminogroups; wherein each n is independently an integer from 0 to 4 and eachR⁶ is independently chosen from each other; d) alternatively, R⁴ and R⁵,together with the nitrogen atom to which they are attached, form a 3- to7-membered aromatic or non-aromatic cyclic group containing from 1 to 4heteroatoms chosen from N, O and S, wherein said 3- to 7-memberedaromatic or non-aromatic cyclic group is optionally bridged and/or fusedto another 3- to 7-membered aromatic or non-aromatic cyclic groupcontaining from 0 to 4 heteroatoms chosen from N, O and S; wherein eachof the cyclic groups is independently optionally substituted by one ormore substituents chosen from —(CH₂)_(n)R⁶ and R⁷; wherein each of thehydrocarbon chains and each of the cyclic moieties of the R⁷substituents is independently optionally substituted by one or morefurther substituents chosen from —(CH₂)_(n)-R⁶ and R⁸; wherein each ofthe alkyl chains in the R⁸ substituents is independently optionallysubstituted by one or more further substitutents chosen from—(CH₂)_(n)-R⁶, hydroxy, halogen, alkoxy, alkylthio, amino,monoalkylamino and dialkylamino groups; wherein each of the R⁶substituents is independently chosen from each other or an N-oxide or apharmaceutically acceptable salt thereof.
 2. A compound according toclaim 1, wherein each of R¹ and R² independently represents: a) an alkylgroup optionally substituted by one or more substituents chosen fromhydroxy, halogen, alkoxy, alkylthio, amino, monoalkylamino,dialkylamino, hydroxycarbonyl, and alkoxycarbonyl groups; or b) a groupof formula —-(CH₂)_(n)-R⁶, wherein n is an integer from 0 to 2 and R⁶represents a 3- to 7-membered aromatic or non-aromatic cyclic grouphaving from 0 to 2 heteroatoms chosen from nitrogen and oxygen.
 3. Acompound according to claim 2 wherein R¹ and R² are both unsubstitutedC₁-C₆ alkyl groups.
 4. A compound according to claim 1, wherein R³represents hydrogen or a halogen atom.
 5. A compound according to claim1, wherein R⁵ is hydrogen, a group of formula —(CH₂)_(n)R⁶ or ahydrocarbon chain chosen from alkyl, alkenyl and alkynyl, wherein saidhydrocarbon chain is optionally substituted by one or more groups chosenfrom —(CH₂)_(n)-R⁶ and —(CH₂)_(n)-O—R⁶; wherein each R⁶ is independentlya phenyl or a pyridyl group, and wherein each R⁶ is independentlyoptionally substituted by one or more substituents chosen from halogen,hydroxy, alkyl, alkoxy and alkylthio groups.
 6. A compound according toclaim 5, wherein R⁵ is hydrogen or an alkyl group.
 7. A compoundaccording to claim 5, wherein R⁴ is a) hydrogen; b) a group of formula—(CH₂)_(n)-R⁶ wherein n is 0, 1 or 2 and R⁶ is a 5- to 6-memberedheteroaryl or heterocyclyl group containing up to 2 heteroatoms chosenfrom N, O and S, wherein R⁶ is optionally substituted by a R⁷substituent chosen from alkyl, alkoxy, arylalkyl or heteroarylalkylgroups, wherein each of the aryl and heteroaryl moieties of thesearylalkyl and heteroarylalkyl R⁷ substituents is independentlyoptionally substituted by 1 or 2 further R⁸ substituents chosen fromhalogen, cyano, alkyl, trifluoromethyl, alkoxy and alkylenedioxy; orc)an alkyl group, which is optionally substituted by 1 or 2 substituentschosen from amino, monoalkylamino, dialkylamino, —OR⁶ and —SR⁶substituents, wherein R⁶ is a 5- or 6-membered heteroaryl groupcontaining 1 or 2 heteroatoms, and is optionally substituted by one ormore R⁷ substituents chosen from hydroxy, halogen, amino,monoalkylamino, dialkylamino, cyano, hydroxycarbonyl, alkoxycarbonyl,alkoxy, alkylenedioxy and alkylthio; and wherein the alkyl chains ofeach of the said monoalkylamino and dialkylamino substituents areindependently optionally substituted by 1 or 2 further substituentschosen from a hydroxy group and a group of formula —(CH₂)_(n)-R⁶,wherein n is an integer from 0 to 4 and R⁶ is an aryl group.
 8. Acompound according to claim 1, wherein R⁴ and R⁵ form, together with thenitrogen atom to which they are attached, an optionally bridged 5- to7-membered aromatic or non-aromatic cyclic group, which contains up totwo nitrogen atoms, and which is optionally substituted by a group offormula —(CH₂)_(n)-R⁶ or by a R⁷ substituent chosen from alkyl, alkenyland alkynyl chains; wherein each of said alkyl, alkenyl and alkynylchains is independently optionally substituted by one or more groups offormula —(CH₂)_(n)-R⁶ or R⁸ substituents chosen from hydroxy, halogen,alkoxy, alkylthio, amino, monoalkylamino, and dialkylamino groups;wherein each of the alkyl chains in these R⁸ substituents isindependently optionally substituted by one or more further substituentschosen from a group of formula —(CH₂)_(n)-R⁶, and hydroxy, halogen,alkoxy, alkylthio, amino, monoalkylamino and dialkylamino groups;wherein each of the R⁶ groups is independently chosen from each other.9. A compound according to claim 8, wherein R⁴ and R⁵ form, togetherwith the N atom to which they are attached, a 5-, 6- or 7-memberedsaturated heterocyclic group, which contains 1 or 2 nitrogen atoms andwhich optionally carries a bridging alkylene group, wherein saidsaturated heterocyclic cyclic group is optionally substituted by a groupof formula —(CH₂)_(n)-R⁶ wherein n is 0, 1 or 2 and R⁶ is a 5- or6-membered aromatic or non-aromatic ring containing 0, 1 or 2heteroatoms chosen from N, O and S, or by a R⁷ substituent chosen fromalkyl and alkenyl groups, wherein the group R⁶ is optionally substitutedby 1, 2 or 3 further substituents chosen from haloalkyl, alkyl, alkoxy,alkylenedioxy, cyano and halogen groups, and the said R⁷ substituentoptionally substituted by 1 or 2 phenyl substituents.
 10. A compoundaccording to claim 1 chosen from:4-(1,3-Dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-[2-(pyridin-2-yloxy)ethyl]benzenesulfonamide;4-(1,3-Dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-[2-(6methoxypyridin-2-yloxy)ethyl]benzenesulfonamide;6-[4-(4-Benzylpiperazine-1-sulphonyl)phenyl]-1,3-dimethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione;6-{4-[4-(4-Fluorobenzyl)piperazine-1-sulphonyl]phenyl}-1-methyl-3-propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione;6-[4-(4-Benzo[1,3]dioxol-5-ylmethylpiperazine-1-sulphonyl)phenyl]-1-methyl-3-propyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione;6-{4-[4-(3-Fluorobenzyl)piperazine-1-sulphonyl]phenyl}-1,3-dimethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione;1-Methyl-3-propyl-6-[4-(4-pyridin-2-ylpiperazine-1-sulphonyl)phenyl]-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione,4-(1,3-Dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-(2-pyridin-2-ylethyl)benzenesulphonamide;4-(1-Methyl-2,4-dioxo-3-propyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-(2-pyridin-2-ylethyl)benzenesulphonamide;4-(1,3-Dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-pyridin-2-ylbenzenesulphonamide;4-(1,3-Dimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-(6-methoxypyridin-3-yl)benzenesulphonamide;6-{4-[4-(5-Chlorothiophen-2-ylmethyl)piperazine-1-sulphonyl]phenyl}-1,3-dimethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione;6-{4-[4-(5-Chlorothiophen-2-ylmethyl)piperazine-1-sulphonyl]phenyl}-1,3-diethyl-1,5-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione;N-(1-Benzylpiperidin-4-yl)-4-(2,4-dioxo-1,3-dipropyl-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)benzenesulphonamide;4-(1,3-Diethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidin-6-yl)-N-[1-(4-fluorobenzyl)piperidin-4-yl]benzenesulphonamide;or a pharmaceutically acceptable salt or an N-oxide thereof.
 11. Aprocess for producing a compound of formula I as claimed in claim 1,comprising, reacting a sulphonyl chloride of formula II

with the corresponding amine III

and optionally converting the Product of the reaction into thecorresponding N-oxide or pharmaceutically acceptable salt thereof.
 12. Aprocess according to claim 11, wherein the sulphonyl chloride of formulaII is obtained from the corresponding compound of formula IV:


13. A compound of formula II

wherein R¹ and R² each independently represents: a) a hydrogen atom; b)a hydrocarbon chain chosen from an alkyl, alkenyl and alkynyl group,wherein said hydrocarbon chain is optionally substituted by one or moresubstituents chosen from halogen, hydroxy, alkoxy, alkylthio, amino,monoalkylamino, dialkylamino, cyano, oxo, hydroxycarbonyl,alkoxycarbonyl, acylamino, carbamoyl, alkylcarbamoyl,dihydroxvphosphoryloxy and dialkoxyphosphoryloxy groups; or c) a groupof formula—(CH₂)_(n)-R⁶ n is an integer from 0 to 4 and R⁶ represents a 3- to7-membered aromatic or non-aromatic cyclic group containing from 0 to 4heteroatoms chosen from N, O and S, wherein said 3- to 7-memberedaromatic or non-aromatic cyclic group is optionally bridged and/or fusedto another 3- to 7-membered aromatic or non-aromatic cyclic groupcontaining from 0 to 4 heteroatoms chosen from N, O and S; wherein eachof the cyclic groups in the moiety R⁶ is independently optionallysubstituted by one or more R⁷ substituents; R⁷ represents a group chosenfrom halogen, alkyl, alkenyl, alkynyl, aryl, arylalkyl, cycloalkyl,heteroarvl, heteroarylalkyl, heterocyclyl, hydroxy, alkylenedioxy,alkoxy, alkylthio, amino, monoalkylamino, dialkylamino, nitro, cyano,oxo, hydroxvcarbonyl, alkoxycarbonyl, acylamino, carbamoyl,alkylcarbamoyl, dihydroxyphosphoryloxy and dialkoxyphosphoryloxy groups;wherein each of the hydrocarbon chains and each of the cyclic moietiesin R⁷ is independently optionally substituted by one or more further R⁸substituents; R⁸ represents a group chosen from halogen, hydroxy, oxo,cyano, alkyl, difluoromethyl, trifluoromethyl, alkoxy, alkylenedioxy,alkylthio, acylamino, carbamoyl, alkylcarbamoyl, dihydroxyphosphoryloxy,dialkoxyphosphoryloxy, hydroxvalkoxy, Dhenyl, alkoxycarbonyl, amino,monoalkylamino, dialkylamino and hydroxycarbonyl groups; R³ represents ahydrogen or halogen atom, or a nitro, alkoxycarbonyl or alkyl group;wherein the alkyl group is optionally substituted by one or moresubstituents chosen from hydroxy, alkoxy, alkylthio, amino,monoalkylamino, dialkylamino, hydroxycarbonyl, alkoxycarbonyl,acylamino, carbamoyl and alkylcarbamoyl groups; or an N-oxide or aPharmaceutically acceptable salt thereof.
 14. (canceled)
 15. Apharmaceutical composition comprising a compound as claimed in claim 1and a pharmaceutically acceptable diluent or carrier.
 16. (canceled) 17.(canceled)
 18. A method for treating a subject afflicted with apathological condition or disease susceptible to amelioration byantagonism of A_(2A) and/or A_(2B) adenosine receptors, comprisingadministering to said subject an effective amount of a compound asclaimed in claim
 1. 19. A method according to claim 18, wherein thepathological condition or disease is chosen from Parkinson's disease,Alzheimer disease, Huntington chorea, Wilson's disease, asthma,bronchoconstriction, allergic diseases, hypertension, atherosclerosis,reperfusion injury, myocardial ischemia, retinopathy, inflammation,gastrointestinal tract disorders, cell proliferation disorders, diabetesmellitus, and/es autoimmune diseases.